Anti depressants no better than placebos?

September 9, 2016 12:13 PM

After having yet another conversation with a person who helpfully informed me that I should quit my antidepressants and eat kale, I'm curious about this study that 'proves' that anti depressants are no better than placebos.

It raises a lot of questions. Is this 'settled' science? Why did my antidepressant not work until I got a higher dose? Why did I start feeling really down one week until I realized I had filled my pill dispenser up with the old dose accidentally? Why are psychiatrists still prescribing them? For the record, I understand that diet, exercise and talk therapy can also have an effect, but at least for me I needed those along with an antidepressant.

posted by mattholomew to Health & Fitness (28 answers total)

If you have a theory or opinion, you can always find a 'study' that 'proves' your theory or opinion. If you need to feel confident in your opinion, read LOTS of studies.

Anecdata: The first anti-depressant I was ever on fucked me up bad, like worse than if I had never taken it. The second one I went on was a god-send and has made me the functional happy person I am today. I don't think that I all of a sudden subconsciously decided that I wanted to be better on pills and that made the second prescription the effective one. I think, maybe, it was chemicals and science.
posted by greta simone at 12:21 PM on September 9, 2016 [11 favorites]

No, that article is not settled science, not at all. Google will show you various qualified people who disagree with that author vehemently. If your pills help you like my pills help me, then tell the busybodies in your life to quit trying to be your doctor. (If you want to be funny, just say "quit trying to ruin my placebo effect dammit - who made you the placebo police?")
posted by sheldman at 12:22 PM on September 9, 2016 [21 favorites]

Anti-depressants work for some people and not others. And, some people respond to one drug and not another. Some psychiatrists are now doing genetic testing to try to identify who will do better on what medication. Some people also have been found to report a positive, therapeutic-level placebo effect in studies where they were given the sugar pill and not the pill with the active drug in it. It's not a black and white issue. That said, if you're being helped by your current dosage of medication, by all means, keep taking it and don't take health advice from people who aren't your doctor and suggest kale medicine.
posted by quince at 12:26 PM on September 9, 2016 [5 favorites]

"If your pills help you like my pills help me, then tell the busybodies in your life to quit trying to be your doctor."

This.

Seriously, if they work for you, with minimal/bearable side effects, then it really doesn't matter what the meta-analysis says.
posted by brevator at 12:27 PM on September 9, 2016 [13 favorites]

Unless the person who linked you to that study also has a medical degree, I'd disgregard what they have to say about the field of psychiatry. Finding a medication to take is often a crapshoot (I had an almost identical experience to greta simone) but it's decidedly different than not doing anything.
posted by griphus at 12:28 PM on September 9, 2016 [2 favorites]

Here's one way to know this is almost certainly not true: SSRIs have been successfully used to treat anxiety in dogs. Since animals do not understand what medication is supposed to do, they can't be subject to the placebo effect, so it's pretty clear the meds do something.
posted by Ragged Richard at 12:28 PM on September 9, 2016 [36 favorites]

One research study can't "prove" anything, it can only add to an existing body of evidence or start a new one for new lines of inquiry. The research about the effectiveness of antidepressants (I assume you mean SSRIs) over placebos is fairly new so no one can say with any certainty that there is no difference in efficacy between the two.

My (totally uniformed not-a-scientist) opinion is that SSRIs DO have effectiveness over placebos, but that effectiveness is only true for a subset of people who have been diagnosed as depressed, which is a pretty broad label that is given to people who present with similar symptoms from very different origins. Knowing which kinds of depressed people will respond to which SSRIs and which won't respond to any isn't something medical or pharmaceutical science is at all ready for at this point in time.
posted by scantee at 12:32 PM on September 9, 2016 [3 favorites]

If something is working for you, it's working. I tell people who try to give me that kind of advice that you could not have paid me to believe I would have taken any kind of psychiatric medication until I actually experienced depression and PTSD. I now take two antidepressants for mood and an antipsychotic to sleep. I've also had three rounds of ECT. (I spent a number of years working on 9/11 and fell apart afterwards). There is a difference between dysthymia and depression. And research results on medications are different for the two disorders. I say that if it works for you, who cares why it works? It's not you job to justify your choices to a kale fan. My daughter went to a Waldorf school and everyone there felt that way about medicine (and kale) but the also believed vaccines cause autism and fairies are real.
posted by orsonet at 12:50 PM on September 9, 2016

Have we established that the placebo effect is bad in this case? If it makes you less symptomatic, who cares if it's "really working" on a chemical level? I get that with things like cancer, a placebo effect would be bad (you feel better, but your health is actually worsening). But, with respect to depression/anxiety, if you feel better, isn't that, like, the whole of the issue? Not trying to say that depression/anxiety do not have physical/chemical causes or that there are not risk factors with ineffective treatment; but for these illnesses, how do you distinguish between placebo effect and "real" effect? And does that distinction actually matter in terms of health outcomes?

If the meds make you feel better, you can afford them, and you're not experiencing negative side effects, then it seems they work for you, regardless of whether they're placebos. Maybe the kale is a placebo; might want to ask your friend for the peer-reviewed articles supporting the non-placebo effects of kale in the treatment of depression. And is it cooked kale or raw kale or kale tablets of some sort? In what quantity and frequency? Did they account for compounding factors like pesticide use?

To quote Fiona Apple: "He said 'It's all in your head!' and I said 'So's everything.' But he didn't get it."
posted by melissasaurus at 12:51 PM on September 9, 2016 [5 favorites]

Why are psychiatrists still prescribing them?

Because they work life-changing wonders for a lot of people (like me), often with minimal side effects.

My response to people like this is to ask if they would offer a cancer patient unsolicited advice on whether they should do chemo or radiation or not. It's a bit dramatic, but serious depression (which I luckily don't have) is a life-threatening disease for a lot of people. You can cherry-pick "studies" to "prove" just about anything, including your pre-existing Stone Age Scientology-infused prejudices against psychiatric medicine, but it's not valid in any way. Yes, SSRIs work better for some than others. Yes, there are side effects. Yes, it's hard to know which one will work for any given patient. These are all knoan facts about SSRIs, along with pretty much every other drug.

That's why there are psychiatrists who are, among other things, medical doctors, and who devote their lives to figuring out how to help people with, among other things, these drugs.
posted by drjimmy11 at 12:52 PM on September 9, 2016 [2 favorites]

A note on terminology: science doesn't really talk about "proof" - that's for theorems in mathematics.

Scientists talk about evidence. Science works by investigation of falsifiable claims.

The article has "prove" in two places.

"Needless to say, our meta-analysis proved to be very controversial." -and- "The serotonin theory is as close as any theory in the history of science to having been proved wrong"

I wont comment on the actual science here, but I suggest you try to stop thinking in terms of proof, and start thinking in terms of evidence.
posted by SaltySalticid at 1:03 PM on September 9, 2016 [4 favorites]

My response to people like this is to ask if they would offer a cancer patient unsolicited advice on whether they should do chemo or radiation or not.

Oh believe me, people actually do that. And as someone who is on both antidepressants AND chemo, both demonstrably work, and those people are assholes. :)
posted by MsMolly at 1:10 PM on September 9, 2016 [7 favorites]

After having yet another conversation with a person who helpfully informed me that I should quit my antidepressants and eat kale

I'm going to share with you an anecdote of my childhood.

My dad enjoys buying shampoo. Growing up the shower was always full of different varieties and brands of shampoo--volumizing! clarifying! three in one!--whatever, you name it. (I think it's because my dad grew up poor and having a magnificent wall of shampoo splendor to choose from was novel and fun for him, but I digress.) Anyway, one day he was at Walmart standing in the shampoo aisle when he ran into someone he knew--a mom of some girls who went to my school. Her daughters were both several years older than me and shiny popular cheerleader types with salon blonde hair, just like mom. I was not so fancy and my thick thick hair was often a huge tangled mess at the end of the day. Small school, this was not a secret.

So there my dad is in the shampoo aisle when this lady walks up. She assumes he's clueless dad trying to shop for his daughter (and not the shampoo consumer savant that he is) and steps in to offer some advice. "Trying to find a shampoo for phunniemee?" "Sure," he says. "Well," she says, busying herself along the aisle, "she should also be using some styling products. Does she know how to blow dry her hair? Does she have a flat iron? They have a line now that's activated by heat styling--here, this is what Amy and Katie use," and hands him a bottle.

My dad looks at it and says, "is this going to turn my daughter's hair some horrible shade of blonde?"


My point is, it might be socially maladaptive but if someone gives you unsolicited advice, especially unsolicited advice that's condescending and stupid, you can be rude to them.

If some non doctor person told me to quit taking a medication that was helping me and replace it with kale, I think my response would be closer to "idk, will it turn me into a sanctimonious jerkoff like you?" than to think they might be correct.
posted by phunniemee at 1:11 PM on September 9, 2016 [24 favorites]

nthing what SaltySalticid said very neatly. There is no "settled science", just overwhelming evidence.

And don't forget the crucial distinction with medicine in particular: there are two significant and different things to consider. One is whether it works *for you*. If whatever you want to do works for you, then stick with it and tell everyone else to keep their noses out. It's great for you but purely anecdotal for everyone else.

The second thing is the body of scientific evidence. All medicine works in the same way: they offer, for a significant number of people, enough of an up-side to be worth the potential down-side. This is the case for everything from open-heart surgery to an aspirin. Gaining this evidence requires double-blind studies (if possible) and proper analysis. SSRIs easily cross this line for an enormous number of people. But you would have to look hard to find a drug in which you don't get any conflicting studies.

That's not to say that kale might work better for you, of course. But what you're saying about not realising that you were on a lower dose accidentally is confirming that they seem to be working for you, as they do for most people who need them.
posted by tillsbury at 1:20 PM on September 9, 2016

Yeah, the consensus I've seen is that they work REALLY WELL for about a third of those who are prescribed them, and we don't know why they work for that 30% and not the other 70. They just do. Sounds about right, IME.
posted by listen, lady at 1:22 PM on September 9, 2016 [3 favorites]

Ordinarily Well does a fabulous job of talking about the science behind antidepressants. It marries clinical experience and research, and takes a critical eye to oft-cited research. The author (a psychiatrist) very much discusses the specific article you're linking to, even.

The science is not settled, but there's an overwhelming amount of evidence that antidepressants do benefit people. Identifying these people may take some research. How we measure that benefit also takes some research. (For example, the article you link uses the HAM-D scale as a measure of depression -- Kramer goes into the history of the HAM-D and when it works well and when not so well.)
posted by quadrilaterals at 1:31 PM on September 9, 2016 [7 favorites]

FWIW, I once had an acupuncturist during the beginning of the kale craze tell me that there are compounds in kale that cause depression. Relating this anecdote to let you know all sorts of opinions are out there!

I think being nutritionally deficient contributes to not feeling well physically and emotionally, so I have zero doubt that eating healthier in general is beneficial...

Obviously there is a belief or study to prove anything. If whatever you are doing works for you, keep at it. If you want to tweak your diet, this is OK. I'm not sure confusing one for the other is accurate. It's OK to thank someone for their concern or info and then move on to other topics.

Hope that helps.
posted by jbenben at 2:04 PM on September 9, 2016

"If you have a theory or opinion, you can always find a 'study' that 'proves' your theory or opinion."

If I understood her usage correctly, I believe Jessamyn called this confirmation bias.
posted by Lynsey at 2:11 PM on September 9, 2016 [1 favorite]

It is true that antidepressants work in very complicated ways that are not well understood, and that some of the research promoting them is flawed, and that negative studies get buried, etc. But since the initial backlash a more nuanced understanding is emerging, namely that certain types and more severe manifestations of depression respond more strongly to medication than previously thought, and that evidence for alternative treatments such as therapy and exercise have similarly smaller effect sizes when subjected to the same type of meta analyses as has become well known for SSRIs.

Interestingly, when researchers evaluate efficacy by asking simply "do you feel depressed" medication seems to have a much larger effect size than traditional less direct measures like ham d or bdi.

No sources because I'm on phone but you can find a well sourced discussion on this in the recent Fresh Air archives.
posted by mikek at 2:26 PM on September 9, 2016 [3 favorites]

Best answer: Regulatory toxicologist chiming in. I work in the space that involves assessing drug candidates for purity, potency, safety, and efficacy as mandated by the FFDCA and other statutes related to it (i.e. what companies have to prove to the government before they can legally market a drug that makes health claims). I'm refraining from reading other responses.

This is far from settled science, but what is settled in general terms is that antidepressants as a class of pharmaceuticals are not narrowly focused, targeted treatments. They act broadly, and idiosyncratically in different people. We don't understand the therapeutic mechanism of action for most drugs in this class, although we can assess the self-reported effects and some of the physiological effects (especially the short term ones) that people experience while taking them. As a consequence, this kind of therapy is grounded in trial-and-error.

Over time, an increasing number of drugs (not just antidepressants) are discovered to have side effects that are undesirable enough to force drug companies to either alter their product claims and labeling (like putting on a black box warning) or to withdraw a product from the market entirely. This is a symptom of our poor understanding of the very specific physiological/physicochemical systems that mediate mood, personality, and consciousness.

Some doctors do not prescribe specific drugs. Some do not prescribe any at all. Some overprescribe. Some prescribe for conditions that have no clinical support ("off-label"). Most prescribers fall in the nebulous region between these categories. It's complicated.

It's so complicated that there's a literal paradigm shift happening in the world of toxicology. Not just because of antidepressants, but because almost all drugs are faced with this problem to some degree.

Happy to answer more specific questions by memail if you have any.
posted by late afternoon dreaming hotel at 2:26 PM on September 9, 2016 [18 favorites]

Response by poster: Thank you all for your answers so far. To clarify, I'm in no danger of stopping meds. When given unsolicited advice I have no problem telling people to buzz off. I'm looking for a counterargument against this study in particular. Keep 'em coming!
posted by mattholomew at 2:41 PM on September 9, 2016

I would echo much of what LADH wrote a post or two ahead of me. Let's face it - this is a touchy subject. For some, SSRIs seem to "work," or do something, that makes them feel "better." (Forgive all the quotation marks.) It's awfully hard to tell them anything about SSRIs that may be contrary to their positive experience. But, there are many questions surrounding these drugs and many experiences that are counter to the "They are wonderful" testimonies.

Science? I always say that when things are written along the lines of, "It's not known how," or "We don't know exactly why..." that we have, by definition, questions.

Some are convinced Serotonin plays a big role in depression, others aren't so sure. Some think Dopamine plays a much larger role. Some are honest and say, "We don't really know what the hell is going on with depression; lots of theories, no real evidence of what is actually happening. As long as that's the case, all these drugs are like eeny, meeny, miny, moe." And that's just the truth.

As anyone considers psychopharmaceuticals, they should remember that we are in baby stages of understanding depression. Many doctors will use the old, "Well, some people need insulin for diabetes, you just need...," and this argument is ridiculous. We know what is happening with diabetes, we can measure blood levels, we know exactly what insulin does. There is no comparison to diabetes and depression. If your doctor insists it's a proper analogy, ask them when you can come in for a blood test to see if your brain chemistry is within a healthy range.

Bottom line: SSRIs seem to work for some, not for others. They also cause a physical dependence that is extremely difficult to get off of for some, not for others. These things cause horrible side-effects in some, not in others. If the phrase "Your Mileage May Vary," applies to anything, it is the use of SSRIs for depression.
posted by Gerard Sorme at 5:30 PM on September 9, 2016 [2 favorites]

Cochrane reviews are the good standard for evidence, and good news, they've liked at antidepressants very thoroughly. here is one review , for example, that concludes that they are effective. Cochrane reviews look at multiple studies to draw conclusions. Best of luck.
posted by smoke at 6:42 PM on September 9, 2016 [4 favorites]

I found this article a good short summary of the evidence (as at mid-2014). Helped me to understand some of the issues around measurement & sub-populations.
posted by yesbut at 9:39 PM on September 9, 2016 [1 favorite]

Response by poster: Melissasaurus the problem with using actual meds as a placebo is that I do worry about the long term effect on my body and brain and some of the side effects aren't experienced until you go off them. I'm on Venlafaxine and it is brutally difficult to wean off of. It scares me to think what would happen if it was taken off the market and I had to go cold turkey.
posted by mattholomew at 8:11 AM on September 11, 2016

It scares me to think what would happen if it was taken off the market and I had to go cold turkey.

Your prescribing doctor would likely switch you to a different SNRI. If all SNRIs were taken off the market for some bizarre reason, then they'd likely switch you to a different type of medication that affects serotonin and norepinephrine.

The link that yesbut posted talks about weighing side effects and efficacy. All medications have side effects, and all doctors and patients have to basically weigh the negatives of the side effects against the negatives of not treating the underlying condition. There's trade-offs either way -- and with depression, not treating it can be severe.
posted by lazuli at 8:23 AM on September 11, 2016

Response by poster: lazuli, what I'm saying is that the side effects from withdrawal from venlafaxine are so horrible that I worry what would happen if I had to either stop it or go to another drug. As far as I know you can't halt venlafaxine withdrawal symptoms by switching to another similar drug. Certainly all medications have side effects, but if depression meds aren't any better than a placebo then it would theoretically be better to take a sugar pill that has no side effects, no?
posted by mattholomew at 8:29 AM on September 11, 2016

Certainly all medications have side effects, but if depression meds aren't any better than a placebo then it would theoretically be better to take a sugar pill that has no side effects, no?

Yes, but antidepressants are better than placebo, so it's a moot point. Also, many people do experience side effects on placebo; the last study results I saw for a new antipsychotic medication showed that there was twice as much weight gain on placebo as there was on the medication.

This is sounding like something it may be worth talking to your prescribing doctor about. I stopped taking an SNRI when I got to a place where it felt as if the side effects were more of a problem than the depression (because I had made a LOT of changes in my life that put me in a much happier, healthier, stable place). That worked for me, but I also know there are lots of people who need to stay on their medications for the rest of their lives, and that's ok, too. Everyone's situation is going to be different. Your prescribing doctor can help you figure out what makes sense for you.
posted by lazuli at 2:35 PM on September 11, 2016