What the Media Misses About Antidepressants

A new meta-analysis of research on modern antidepressants -- some of it unpublished by the drug companies -- suggests that the drugs have little advantage over placebos.

Why then do so many people consider drugs like Prozac to be miracle drugs for depression -- many putting up with serious sexual side effects in order to take them? Are they simply being duped by a placebo effect or avoiding withdrawal symptoms? And how could drugs which are little different from placebo also produce suicidal or even homicidal thoughts in some patients?

The answer reveals a key flaw of randomized clinical trials and meta-analyses: when you are looking at aggregated data, huge individual differences can be washed out. For example, let's imagine a drug that causes people with one genetic variation to have a profound positive effect -- but causes those with another to get dramatically worse and has little effect on everyone else.

A clinical trial could easily find that this drug has no advantage over placebo, depending on the proportion of people with each gene in the study. Another study of the same drug might find it to be a blockbuster -- while another found it dangerous. Same drug, different populations.

Indeed, researchers looking at antidepressants find exactly these results, according to researcher David Healy, whom I interviewed a while back for Reason. Healy is not known as a drug company booster -- his most recent book is titled Let Them Eat Prozac: The Unhealthy Relationship Between the Pharmaceutical Industry and Depression. It is widely believed he was not hired at one academic job because of his strong views on these medications.

But he continues to prescribe them because the right drug in the right person can be lifesaving.

Some people are strong responders to one drug -- but give them another in the same class, and they become actively suicidal. Most people have a slight positive effect; some have a slight negative effect. In aggregate, a drug that is a home run for one person and potentially fatal to another looks inert.

This doesn't mean that we don't need randomized clinical trials or meta-analyses: RCT's are the gold standard of evidence-based medicine with good reason. But it does mean that until we can better understand how genetic variation affects drug response, we will continue to have these boring debates about Prozac: Angel or Devil.

Especially in a context where the media often refuse to explain how ideological biases affect people's positions on these medications and conveys the story as a clash between two conflicting views of the world. Both sides are right -- but only about the response of particular people to particular drugs. This is why it can be true both that 80% of depressed people can find a medication that works and that clinical trials don't find these drugs much better than placebo when looking at the general population of depressed people.

Cross-posted from Scientific American's 60 Second Science

Comments

[LeoMarvin]

For anyone interested in this subject, this is a useful post with important information. But based on the paucity of comments, I'll bet there are lots of very interested people who just couldn't be bothered reading something that might challenge their firmly held groundless beliefs. It's sad.

[Chatto]

If you spent any time working in the mental health field before the 1970s, you would realize that the advent of psychotropic drugs and anti-depressants are a godsend. Depression is a biochemical disorder, and in its severe forms, no manner of talking cure, job change, or even societal shift can alter its progress. So, unless you'd like to go back to the "snake pits" of the pre-1970s, then you might want to recognize that drug therapy is the best thing that we've got right now to offer relief to severely ill individuals.

[anfractuous]

How you feel is not important, as long as you remain a productive member of society. The purpose of antidepressants is to keep the wheels of industry spinning, no matter how degrading, unrewarding, or numbing your job is.
Your life now has a purpose: trying to climb out of, and remain free of depression. Hey you! Back to work!

[zizyphus]

There are some things about anti-depressants that people don't know. One is that some of them can bring on bi-polar illness. There are new categories of bi-polar now to accommodate this fact. So, if you were just depressed, and took, say, Welbutrin, you might develop bi-polar depression as a side effect. Now, instead of just being sad and apathetic, you could look forward to episodes of mania.

Another is that in the old days, opiates were prescribed for depression. In fact, for some they are the best anti-depressants, That is why some people wind up getting dependent on them, they finally feel not "high" but just normally good. I believe these are individuals who never had the right amount of neuroreceptors to ever really feel happy in life.

Having used both, I can say that any opiate provides a better effect than the modern anti-depressants.

With either substance, abrupt cessation will result in apathy and sadness. The modern anti-depressants are especially devious, as sudden cessation can cause a very profound depression. In some cases, the modern antidepressants like Venlafaxine are molecularly nearly identical to synthetic opiates such as Ultram, which has a horrifying withdrawal period. I was prescribed Ultram for arthritis and found that it was a very effective ant-depressant- I also found it took a long time to taper off using it.

Also, I agree that vigorous exercise is the way to defeat depression, but for those already flattened by the illness, they need something to get them up out of bed so they can start moving. Just remember that whether you choose opiates or a modern anti-depressant, you have to cut back your doses gradually until you are taking an 1/8 of a pill a day before you can quit.

[Northstar808]

Thank-you for your great info. I would like to hear more of what you have to say about prozac. My 16 year old son just started taking it, and I would like to look at different options. Thank-you, [e-mail]

[middleofnowhere]

thank you for putting into words what the majority of people were not considering.

[OneWoman]

I used to sell central nervous system drugs. What some people fail to realize is that it is not the drug that "cures" depression, it's your body's response to it (i.e. down or up-regulation of receptor sites on the neurons). This is why there is such variability in outcome from person to person. I recall reading research that found 30 minutes of aerobic exercise 3X a week to be just as efficacious as Prozac for moderately to severely depressed patients. That took the wind right out of my sails (sales, LOL).

I question our reliance on psychotropic medications. Oftentimes, pills are used as the first line of defense and little or no thought is given to making changes in one's life and/or thinking patterns. Consider this: Every emotion has its own unique chemical signature. Each time you feel sad, it is because the chemicals for "sad" have been released throughout your body. If you think sad thoughts, you end up feeling sad; so if you change your thoughts, you stand a good chance of changing your feelings. (This is the basic premise of cognitive behavioral therapy.)

Research tells us that individuals diagnosed with depression tend to have negative thinking patterns (one can argue the chicken/egg thing here I suppose). Perhaps one of the reasons why antidepressants do not consistently work is due to the following process: A person frequently thinks depressing thoughts and s/he frequently feels depressed. This means s/he has an increased number of receptors on his/her neurons in order to process the "depressed" chemicals and feel depressed. Now, s/he takes an antidepressant, which blocks those depression chemicals from reaching the receptor sites; those sites, in turn, down-regulate, or close up shop because they are no longer needed. HOWEVER, the person continues to think depressing thoughts because it is a HABIT, so more "depression" chemicals are released, which leads to more receptor sites being needed... This could be why antidepressants seem to lose their effect over time. Something to consider...

[January]

The difference between lab tests and prescribed use is that the doctor says, "Here's what it is supposed to do." That is, if it doesn't work for you, report back to me.

So lab tests are only to establish the "here's what it's supposed to do."

Medicine is an art not an assembly line. Journalism, on the other hand, is supposed to be an art but has turned into a business--whatever gets you published.

[NABNYC]

Let's assume that the drug companies were non-existent, or had no incentive to create new "needs" for drugs.

If we had many people reporting problems of depression, wouldn't we start by examining what is going on in their lives, and what is going on in society? Do we have more depression today than existed 100 years ago? Do the chemicals in our food create depression?

What about the lack of community that is now the norm in the U.S. I saw a great documentary on the 3rd ward in Texas (Houston?), a little neighborhood of tiny homes that have been taken over by a group of artists, renovated, made available for single moms, kids, artists, and a new vibrant community has sprung up. Did I mention this was mostly a black area? Child-care, child after-school courses, rent and home buying assistance, support for people to go to school, get skills. Community.

The average suburban neighborhood has no community. None. That's one of the reasons people flock to churches, because they don't know their neighbors, or their neighbors keep changing, and they basically have nothing in common. Their kids don't go to the same school, they don't even work in the same area.

Anti-depressants are big business. Just like hormones were for menopausal women, until it was disclosed that they caused cancer.

The idea that drugs can solve our problems or improve our lives is lucrative for the drug companies. And undoubtedly for people with serious depression, drug therapy might save lives.

If insurance and drug companies didn't run the whole system, I think we would prescribe diet changes, exercise, other activities, long-term counselling, possibly group counselling as well, before turning to drugs. We give drugs to our "problem" children, to our depressed adults, sleepless seniors. Are things getting better as a result? Or worse?

Are we all just manchurian candidates willing turning our brains over to industry? Is there any reason we should trust the drug companies? How many people have they killed? How many test results have they fudged or hidden?

Why should we trust this industry which pays so many bribes to our politicians? What protection are they paying for? Well, for one thing, they want Congress to make it impossible for anyone to sue a drug company if they take the drugs and die. Isn't that good enough reason to be very suspicious of these people?

[marignymitch]

Ms Szalavitz:

I suffer from clinical depression and PTSD and currently am taking four drugs, one strictly for PTSD, to treat my illnesses.

I am not cured but I am also no longer chronically depressed, suicidal, hopeless, compulsive, negative, sleepless, angry or plagued with anxiety. I'd say my meds are working.

[nainam97]

I think the most interesting, and amazingly unexplored, thing about drugs is how differently they affect different people.

It's really important to figure this out. So that tests of how drugs work can take this into consideration.

For example: The ingredient in Benedryl and similar OTC sleeping or allergy aids happens to make me extremely hyper. It literally makes my heart race and totally guarantees that I will NOT sleep instead of vice versa.
(Plus, instead of stopping my sneezing it makes me sneeze!!)

Yet for my sister, genetically very close to me, 1/2 half a tablet of Benedryl is enough to knock her out for 8 hours.

Go figure!! I think the drug makers and drug testers need to start taking this sort of thing into consideration.

[zaneblue]

Bipolar disorder and moderate depression are caused in part by malnutrition. The level of omega-3 fatty acids is too low. This has a profound effect on brain function.

Of course there is a time and place for antidepressants, but many depressed people would improve remarkably by getting a half hour of moderate exercise in the sunshine every day and taking 1600 mg of EPA and 800 mg of DHA every day (check with your doctor for drug interactions, do not take high-dose fish oil like this if you are on blood-thinners, take a lot of OTC pain relievers, are scheduled for surgery, are allergic to seafood or have a defibrillator).

[tbone99]

okay- so when does Ton Cruise get an apology?

[mcthfg]

Thanks, Maia, for your unflinching looks at drugs and drug culture. Your articles always contain something that so many others covering this topic seem to lack - common sense.

[lillianjane]

Yes, and thanks for explaining this so I understand where those misleading headlines come from. They are fodder for all the people who have never been depressed but are sure they know that drugs aren't a valid treatment.

[mkexplorer]

This article really hit the nail on the head. By "averaging" the results, we mask the clearly positive results that most depressed people get by trying more than one medication. I got absolutely no relief, and often felt worse overall, with my first three anti-depressants. The fourth - Celexa - was a miracle for me. For the first time in my life, I felt like a complete human being. Yet the previous poster blueraven actually felt much worse on this same drug.
While anti-depressants may be overprescribed in patients exhibiting less-than-severe symptoms, many of us owe our productive lives to these medications. I am afraid that this meta-analysis, combined with a general ignorance of statistics, may lead to unnecessary suffering.

[Guitarsandmore]

I think these drugs are dangerous and create more problems than they cure. I have just seen too many people go down and not come up because they thought the DRUG was the answer to all of their problems.

These drugs won't fix your life. You have to do that through your own actions.

These drugs are for people who would be bipolar, ranting, raving, screaming, sleepless, insomniac, lunatics without them.

If you are sad or lonely don't go down this road of heavy medication. Its not for you.

[lillianjane]

Anti-depressants are for depressed people. Depression doesn't make you any of those things you mention.

[Guitarsandmore]

I live with someone who is all of those things when she doesn't get her "anti depressants" so you will never convince me of your statement.

What I find especially troubling is how easily doctors will prescribe medications and for just about any reason you can come up with. You don't have to be depressed.

The best use I have seen for drugs is to get you over a temporary rough spot such as anxiety over and upcoming surgery or something similar and then quit the drug ASAP.

The other troubling thing I see with doctors is their "one size fits all" as far as dosage requirements go. Not all doctors think so narrowly but a fair amount will try to get you to take a certain dosage because it is the minimum effective dosage amount or some such nonsense. People are not one size fits all. What drug works for you might not be of any use to me and the same with the dosage. You have to learn your own body and what it can tolerate. Don't let the doctors bullshit you.

[blueraven]

I've found this variation to be true for me. Much to my psychiatrist's amazement, Celexa gave me panic attacks. He switched me to Zoloft, and that has had a slightly less pronounced positive effect on my depression but hasn't triggered the attacks. Meanwhile, a friend of mine considers Celexa to be the single best thing she's found to keep her from jumping off a bridge. The failure to grasp how drugs can play havoc on a minority of people was accidentally expressed by one of the pharmaceutical assistants at the drug store where I noted the problem while asking to have the Celexa scrip disabled in my history. She was quite sure the problem had to stem from an inert ingredient in the generic version.

[fisharefreinds]

"while asking to have the Celexa scrip disabled in my history"

Why? Insurance companies black flag this. Until we look at all the reasons for the epidemic of depression in our present day society--and it is at alarming rates today--what will we accomplish? It is like trying to find the cure to cancer without taking into account the world we live in. We can self-talk, and that is extremely helpful; we can medicate and that helps some; but there is so much to be depressed about now, even hiding history of medications from Insurance companies....