Antidepressants vs. The Placebo Effect: Whether SSRIs Really Work

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postpartum depression

© Fotolia - photo-Dave

This past Sunday, CBS’ 60 Minutes aired a segment on antidepressants being no better than placebo.  Harvard researcher and author Irving Kirsch says antidepressants do not work because of the ingredients inside them or any effect they have on serotonin, but because we believe we’ll get better when we take them. We could just as easily be taking a sugar pill, without knowing it, and we’d get the same effect, he argues.

If you saw the story, you might be feeling very confused right now. Even Lesley Stahl, who reported the story and whose husband takes an antidepressant, said she was confused.  Kirsch and others interviewed were very confident that SSRIs don’t have the impact that pharmaceutical companies would have us believe.

I take one. It seems like it works for me. Yet does it really? Am I just fooled into believing it works?

John Grohol, editor-in-chief of Psych Central, responded, “What wasn’t mentioned in the 60 Minutes piece, because it was opinion journalism forwarding a specific viewpoint, is that Kirsch’s research is selective. He hasn’t looked at every antidepressant study ever done (now numbering in the thousands). He only looked at the clinical trials required to gain U.S. Food and Drug Administration approval for 6 antidepressant drugs (there are over a dozen on the market).”

I reached out for input from Dr. Marlene Freeman of the Massachusetts General Hospital Center for Women’s Mental Health for input as it applies to women with postpartum depression — well, everyone really, but my focus is women with postpartum depression — and I want you to see her response. It really helped me to understand the placebo effect better and why people like Hirsch make the claims they make:

The gold standard in the research of medications is the randomized, placebo-controlled trial. This means that patients enter a research study, and receive either the treatment being studied (such as an antidepressant) or a “fake” or placebo pill (one that has no active ingredients). The reason that studies are placebo-controlled is that the act of participating in a study itself is huge, and patient expectations also can influence treatment outcomes. [so it's better if patients don't know what they are getting]

In a typical, real-world setting (not a study), a patient decides to pursue or not pursue treatment, and if she selects treatment she picks herself she carries with her expectations about that treatment. In a clinical trial of an antidepressant for depression, patients enter the study and are thoroughly evaluated. They usually have blood work and hours of communication with study staff from the start of the study and then regularly (for example, every two weeks throughout the trial).  Studies usually take place in clinical settings with doctors and nurses, and patients are carefully monitored for symptoms and side effects. Basically, participating in a clinical trial results in a lot of attention for the patient, often more than she would receive in routine care at her doctor’s office, as visits tend to be frequent with a lot of detailed evaluations.

Therefore, it is not surprising that many patients will feel better while they participate in a clinical trial, regardless of whether they receive an active medication or placebo. The goal of an antidepressant trial is to demonstrate that the antidepressant is better than placebo in the particular context of a clinical trial. Placebo response rates in depression studies are historically quite high, between 30 – 50%, meaning that factors other than the fake pill treatment helped patients improve. To show superiority over the placebo, the active antidepressant needs to show statistically more benefit than the placebo group, which can have substantial improvement. A study design needs to factor in the placebo response. Smaller studies are usually less likely to show a benefit of either treatment group compared to another.

It is not unusual for an antidepressant to fail to show statistically substantial benefit over placebo, particularly in smaller studies. In a “negative study,” one in which the antidepressant did not “beat” placebo, it doesn’t necessarily mean the antidepressant is ineffective. The study may just not have been one in which the efficacy of the antidepressant showed up beyond the general benefits of study participation and expectation that both the antidepressant and placebo groups experienced.

The placebo effect raises challenges for studying antidepressants. Huge trials are generally required, which are very expensive. The number of “negative trials” with high placebo response rates also show that antidepressants are only part of the experience patients receive when pursuing treatment for depression. Medication treatment should include thorough evaluation, frequent follow up, support and attention.

Receiving a placebo in an antidepressant study is a far cry from suffering from depression without getting help. Because depression is a serious illness, to purposefully leave a patient without a full evaluation and careful attention and monitoring would be unethical.

I have participated in a research study. It’s true that you get tons of attention and support. Everyone is watching you and talking to you about your problems and how you’re feeling and you feel like you have a team of people behind you.  It’s nothing like what one might expect from regular visits with your primary care physician or another doctor.  It makes perfect sense to me that people participating in a trial, especially if they have mild or moderate depression, would get massive benefit just from the participation alone, regardless of whether they’re getting the active or inactive medication.

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About Katherine Stone

is the founder & editor of Postpartum Progress. She was named one of the ten most influential mom bloggers of 2011, a WebMD Health Hero and one of the top 25 parent bloggers using social media for social good. She also writes the Fierce Blog, and a parenting column for Disney's Babble.com.

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  1. Katherine,

    I feel like you have the gift of reading a postpartum woman's mind…. I too watched 60minutes and was in tears after the segment. I wanted to throw my pills away and start over- it's been on my mind all week- My poor husband was totally confused and had no idea what to tell me……THANK YOU for this piece, I am now more informed and feel better continuing my treatment with medication. I feel like every time I'm on your site I get the answer to one of the many questions that swirl in my mind about PPD!

    What a wonderful site you've created:-)

    Kris

    • Kris, I hope you and ALL of my readers know that if something like that happens — you see or read something about postpartum depression or anxiety and its causes or symptoms or treatments that upsets or confuses you — you can always send me an email and asked me to look into it and write about it for you. That's why I'm here!

      – Katherine

  2. Reading this makes me wish I was in a trial study while I was spending months and months in the depths of dispair trying to find the right med that worked for me. I wish I had ppl checking up on me everyday, b/c if I did, then maybe it wouldn't have taken so long to find the right fit.

    But I know without a shadow of a doubt, that the SSRI saved my life, and if I was given a placebo, then I may not be here anymore!

    • Maura,

      I'm with you. Wouldn't it be nice if more attention and support was the standard of care?

      I think this says something about the docs who whip out a prescription with little to no patient education and no followup and monitoring. That's not okay.

      — Katherine

      • My experience was that the doctor asked me what I wanted her to prescribe. Since I had been on a very low dose of an antidepressant during my pregnancy, I just said what that had been and thought that it would do the job. And as you mention, Katherine, no education, no follow-up and monitoring. Well, turns out I'm not very good at prescribing. It took months to unscramble the mess my world became and to find a competent doctor who not only prescribed on her own judgement but also worked with my therapist.

  3. But doesn't that say something so sad about the state of community. I would have still needed an antidepressant to get through want I went through, but I know I would have felt better if I'd a community of people who cared around me after my son was born. Instead I'm in a foreign country half a world away from my family and my best friends with a husband who was unable to cope and where most women return to work 6-12 weeks after having their babies.

    This, plus the latest parenting book hubub over 'Bringing Up Bebe' got me thinking; what would it be like if the United States had 12 months of paid maternity leave? What if women had options to work part time without losing their health insurance or their place on the ladder? What would it be like if, when I went to the playground there was another mother there?

    Community doesn't solve everything, just as antidepressants don't solve every aspect of depression, but working in combination motherhood might just be a little easier.

    • Lucy,

      You're right. It would be better if we had more pro-parent policies in the US. It wouldn't solve all of our problems, or prevent postpartum depression outright, but it could certainly help.

      – K

  4. If its only a placebo affect, someone sure is making a lot of money off them…and what about the side effects? And in case, I'm glad whatever I'm taking is available to me as no doubt are my sons and husband.

    • Getting each woman the proper support system she needs for her own unique situation is a tall order but one that every woman deserves fulfilled. In the trenches of my ppd I had a tremendous amount of support and top notch professionals, some who made blunders causing more harm than good and others who came along to help pick up the pieces. What helped me most was not only individualized care. But proffessionals who were willing to meet me where I was at with COMPASSION and guide me in the direction I needed to go, no matter how low of a point in my ppd I may have been. Also family, friends and proffessionals who believed in me and had HOPE for me when I had none for myself. That hope carried me a long way when I was not able to stand on my own two feet let alone take a step toward recovery. To those people I am eternally greatful.

  5. It seems like if it were the placebo effect, then the first 2 medications I tried should have worked; instead, it was the third that worked in combination with another medication. I believe I finally found the right medication, not that I suddenly believed in this one more than the first two for some reason.

    • This was my experience too. I was on a mild anti-depressant for years before I got pregnant. When I went through PPD, I went on Zoloft because I was breastfeeding and paranoid about taking anything else. Zoloft helped get me out of the major depression but I never felt good. so then about a year later, I went on Cymbalta, which also "helped" but had so many physical side effects and made me feel edgy that I knew it wasn't working. Finally, I talked to my doctor about going on my original (pre-pregnancy) medicine but at a higher dosage. It's worked wonders.

  6. There's a huge article on this right now on mercola.com. It's fodder for people who think psychiatry is making people sick etc…It disheartens me because its responses like that that kept me from trying medication when I was so sick. Luckily, I was so desperate that I was willing to try anything, even meds!

  7. Placebo effect or not, taking this pill every day keeps me alive. So I'll continue to do so. I have a hard time believing though that it's just a placebo effect. Thanks for posting this.

    • Do you consider the pharmaceutical companies will love to hear someone say this? : -D

      I’m not trying to be Debbie Downer with my messages on here, I sincerely want people to get better. But it doesn’t seem objective when no one seems to want to consider the evidence against SSRIs really working.

      I said it before, there is not a single test available that shows serotonin levels. The whole basis of Prozac and onwards was based on a theory that has never been scientifically confirmed.

  8. Lorita Canu says:

    Like dogs inside a wheel, birds inside a cage, or squirrels in a chain, ambitious men still climb and climb, with great labor, and incessant anxiety, but never achieve the top.

    Every couple of seconds it changes – up an eighth, down an eighth -it's like playing a video slot. I lose $20 million, I gain $20 million.