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Placebos as Effective as Antidepressants


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are antidepressants just placebos, placebos and antidepressants
A study shows antidepressants and placebos are on equal ground in terms of efficacy. iStock.com/Nogueira

THS reader Chad sent in this question:

Antidepressants – effective or placebo?

The use of antidepressant medication has become so widespread and commonly accepted that it seems almost sacrilegious to question it. But alas, questioning is the name of the game here at The Healthy Skeptic!

And what do you know? Antidepressants aren’t all they’re cracked up to be. In fact, a recent meta-review of published studies on the efficacy of antidepressant drugs revealed that selective serotonin reuptake inhibitors (SSRIs), which are the most commonly prescribed drugs to treat depression, have no clinically meaningful advantage over placebo.

What that means is that in most of the trials reviewed, patients who took a sugar pill recovered from depression just as often as those who took the active drug. This study may come as some surprise to both physicians and the general public, whose faith in the efficacy of these drugs has led to over 118 million prescriptions in 2007 and over $16 billion in sales.

But should this really come as a surprise? Antidepressant drugs are thought to act by altering levels of brain neurotransmitters; however, it takes several weeks before these changes can be measured. Yet patients often report symptomatic relief within hours or days of receiving an antidepressant.

Available data suggests, in fact, that SSRIs are no more effective than placebos and have considerable adverse effects and risks, including increased suicidality amongst both children and adults. Sapirstein and Kirsch conducted a meta-analysis of 3,000 patients who received either antidepressants, psychotherapy, placebo or no treatment at all. They found that 27% of therapeutic responses were attributable to drug activities, 50% to psychological factors, and 23% to “non-specific” factors. In other words, 73% of the response to the drug was unrelated to its pharmacological activities – and antidepressants may be no better or more specific than placebos.

This of course raises grave questions about why the National Institute for Health and Clinical Excellence (NICE) still recommends that antidepressants should the be first line treatment for moderate or severe depression. Their message is identical to that of the Defeat Depression Campaign in the early 90s, which contributed to the 253% rise in antidepressant prescribing in 10 years.

In a review published in the British Medical Journal in February of 2006, researchers Joanna Moncrieff and Irving Kirsch point out that the NICE recommendations ignore even their own study data. Although the NICE meta-analysis of placebo controlled trials of SSRIs found statistically significant differences in levels of symptoms, these were so small that the effects were deemed “unlikely to be clinically important.”

After analyzing several published studies and reviews, Moncrieff and Kirsch reached the following conclusions:

Summary Points

  1. SSRIs have no clinically meaningful advantage over placebo
  2. Claims that antidepressants are more effective in more severe conditions have little evidence to support them
  3. Methodological artifacts may account for the small degree of superiority shown over placebo
  4. Antidepressants have not been convincingly shown to affect the long-term outcome of depression or suicide rates

The response to a drug or placebo in a clinical trial for depression is often measured using the Hamilton rating scale, a multiple choice questionnaire which doctors use to rate the severity of a patient’s condition. The questionnaire rates the severity of symptoms observed in depression such as low mood, insomnia, agitation, anxiety and weight-loss; it is considered to be a highly reliable physician-rated scale and has been reported to be more sensitive than patient-rated scales to drug/placebo differences. (Murray, 1989)

In the NICE meta-analysis, the difference between drug and placebo groups was one point. The most commonly used 17 item version of the Hamilton scale has a maximum score of 52. It is highly unlikely that a difference of one point on a 52-point scale is clinically significant, a fact that the FDA has admitted in memoranda (Laughren, 1998; Leber, 1998) reviewed by Moncrieff and Kirsch.

Other studies have yielded similar results. A study by Khan et al. found a 10% difference in levels of symptoms between placebo and active drugs in two different meta-analyses. In a more recent review, Kirsch et al. invoked the Freedom of Information (FOA) act to obtain access to previously unpublished studies (the drug companies are under no requirement to publish a study they have sponsored if the results don’t suit them). The overall difference between drugs and placebos in that analyses was 1.7 points on the Hamilton scale.

Moncrieff and Kirsch also point out that the Hamilton scale contains seven items concerning sleep and anxiety, with each item on sleep scoring up to six points. Therefore any drug with some sedative properties, including many antidepressants, could produce a difference of two points or more without exerting any specific antidepressant effect.

Follow-up studies that track patients for a significant length of time have also shown very poor outcomes for people treated for depression both in the hospital and in outpatient settings, and the overall prevalence of depression is rising despite increased use of antidepressants. Suicide rates have increased in some groups and some countries, despite increased prescribing of antidepressant, and there are continuing concerns that SSRIs may increase the risk of suicidal behavior in obht cildren and adults.

In children, the balance of benefits to risks in antidepressant treatment is already recognized as “unfavorable”. The analyses performed by Moncrieff and Kirsch strongly suggests that the same is the case for adults, and that the ongoing uncertainty about the possible risk of increased suicidality as well as the adverse effects of antidepressant drugs warrant a “thorough re-evaluation of our current approach” to treating depression.

I couldn’t agree more. One question the authors failed to pose, which I believe to be at the root of the matter, is why are so many more children and adults depressed now than before? You might not be surprised to learn that I have some thoughts about this. But I’ll save them for another post.

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Join the conversation

  1. I also disagree with the article. I had acute anxiety and depression with my first pregnancy which was miscarried at 13 weeks and my second pregnancy. At the time I didn’t know anything about mental illness and didn’t figure out what was wrong and start getting treatment until five month into my second pregnancy. At that point I had been averaging 3-4 hours of sleep per night for several months because my anxiety was so severe while I was trying to fall asleep. I was completely disfunctional. I am a mechanical engineer and I was having trouble with basic math. I couldn’t remember the names of my co-workers I’d known for years, etc. When I finally checked myself into the psych unit at the hospital because I was afraid I’d kill myself, they prescribed Zoloft, an SSRI.

    I WILL say there was some placebo effect. The fact that I knew the agony I felt was going to end in a couple weeks gave me hope and helped me have the strength to call my husband when I felt like putting a knife in my chest. But the Zoloft also had a great effect. After being on Zoloft for two weeks I was able to fall asleep without having “nightmares” while lying in bed awake. After three weeks I was completely back to normal except when I got really hungry (which can happen quickly without warning when I’m pregnant) I would panic. They increased my dose and a week later I felt normal again.

    Also, if I forgot to take the Zoloft two days in a row I would notice symptoms about three hours after the second missed dose even before I realized I missed the doses. This happened several times with my second and third pregnancies.

    Mental illness is a medical problem and anybody who says it is a “psychological or social problem” and therefore doesn’t warrant medication obviously doesn’t love anyone who has suffered from it.

    When the doctors at the hospital first gave me Zoloft, I got the impression that it was going to take the edge off. Like that I wouldn’t feel like killing myself, so I could “get through” the last few months of my pregnancy. I can honestly say that the happiest news I have ever received in my entire life was when my subsequent psychologist told me that it should get me back to 100% normal.

    I also had anxiety and depression during my third (most recent) pregnancy and got treatment after only a week of symptoms.

    My sister also suffers from depression during and after pregnancy (although not as extreme as mine) and she refuses treatment because of some of the non-sense like this article that people have told her. Her family suffers greatly for it. Zoloft during breastfeeding is a lot safer than a mother who doesn’t look her baby in the eyes.

    All that being said, I am learning to eat a real food diet. I was eating the USDA-recommended low-fat (i.e. basically devoid of vitamin A and D and inherently high-carb) diet previously. I am hoping that a nutrient deficiency which I can correct was the cause of my anxiety/depression. But without Zoloft I wouldn’t be here to figure that out.

    • Michelle,

      Our stories are somewhat similar, though I have never been pregnant before.

      My depression only began when I started on Depo Provera, many years ago. I blame Depo for causing my depression. There was a period of 2 years of my adult life when I went off all birth control and didn’t need to take my SSRIs. I am currently back on SSRIs because I am now taking a hormonal birth control to prevent pregnancy, which I intend to stop soon. I will be switching to FAM (fertility awareness method: basal body temperatures + cervical fluid). I expect that when I stop hormonal birth control, I will be able to either come completely off the SSRI, or take only 1 pill per week or every other week.

      I believe that your case (depression during pregnancy) was, like mine, caused by hormonal imbalances. And yes diet does help too. Purging out all or most sugars in the diet helps with mood disorders. I am in the process of replacing granulated cane sugar with stevia and erythritol. I like stevia the best so far.

      Good luck in your journey!

      • Thanks for sharing. You have a very interesting story. I wonder if you would be better on a different birth control? I don’t use birth control either because it doesn’t seem worth the other possible side effects (cancer, stroke, etc.) but never had any mental health problems during the 18 months I was on it. We’ve just been using withdrawal for the last five years.

        The doctors did tell me my illness was due to hormonal imbalances. And I believed them. But that doesn’t satisfy me anymore. After I started being more open about my experiences, I have found a striking number of other people who have mental illness, not to mention almost everyone on my street has a child with a disease that requires constant medical treatment (heart arrhythmia, asthma, brain tumors, severe food allergies, ADHD, four out my six cub scouts are autistic, the list goes on), and three of my five closest friends are unable to get pregnant. So I started thinking, “something’s in the water,” so to speak. And the thing that has changed the most over the last century is the American diet. I feel like if my diet was causing my susceptibility to depression during pregnancy, my diet was probably not good for the rest of my health or my children either. So that is what I’m working on. I’ve found a cook book by Sally Fallon called Nourishing Traditions that makes a lot of sense to me and has been very helpful. It is easy to find advice of what not to eat, but Sally explains what is good to eat and teaches you how to prepare the food and even where to buy it.

        Good luck to you too!

    • “Mental illness is a medical problem and anybody who says it is a ‘psychological or social problem’ and therefore doesn’t warrant medication obviously doesn’t love anyone who has suffered from it.”

      Excuse me? Not only did you bypass the faulty premise, which I had mentioned above, but you threw in an underhanded slur against me, without any knowledge of my own history and experiences. I obviously do not love anyone who has suffered from depression? Again, excuse me?

      I have personally suffered from two cases of SEVERE depression to the point I was incapacitated for entire days at a time during this period. The darkness in my mind felt like a true hell that I would never wish upon anyone else. I was able to live through the depression not because of any medication. (A doctor had given me Lexapro, which I never took.) I had a close relative who let me stay at her house for an indefinite period of time for “however long it will take you to get over this.” Just this simple act of genuine human compassion did WORLDS MORE than any doctor’s visit or medicine could have accomplished. I was caressed and enveloped in warmth from not only my immediate family, but also my relatives. We had DEEP conversations about life and death; about purpose and meaning; about my inner self; and even some metaphysical topics. Eventually, I found closure and could let my mind rest at peace. The depression left me after I had I pin-pointed its cause and faced it (through our conversations), and finally found closure to my personal struggles.

      Had I dismissed what was going on in my mind, had I downplayed my feelings, had I believed I was suffering from some “chemical imbalance”, I might have taken antidepressants and hooked myself on a life dependence with risks of withdrawal symptoms.

      I personally know people close to me who have suffered severe depression and contemplated suicide. I have nothing but sympathy for them and I offer myself as a human being to help them in any way possible, unconditionally. I do not coldly write out prescriptions.

      If you want to educate yourself, I recommend the following books:
      Toxic Psychiatry, by Peter Breggin
      Anatomy of an Epidemic, by Robert Whitaker

      I wish you all the best, but I do not engage in extended dialogues when I see the telltale signs of denial, especially when such a cold, underhanded attack is thrown at me.

      Good luck with everything.

      • I don’t think you were mentally ill. It seems as though your depression was triggered by two specific events that occurred in your life, and that you were able to recover completely once you had emotionally and psychologically dealt with the emotional consequences of those events. In cases such as yours, where depression is not ongoing and is not being caused by a chemical imbalance, medication is not appropriate. Your situation is similar to the natural grieving phase when a loved one dies. One would normally not take medication during the grieving period when a loved one dies.

        But in a case where someone has always suffered from depression, or has suffered for a long time from depression, and it is not being caused by any specific event or unhandled emotional business, then it is in fact a true mental illness (meaning, it probably is a chemical imbalance), and ongoing medication is appropriate.

        • Theonat, I didn’t mean to attack you at all. I’m glad you worked through your depression. It is too bad that many doctors hand out prescriptions without taking the time to figure out whether someone has clinical depression or is feeling depressed for a good reason, and which therapy would be appropriate. But the fact that your problem could be solved by a support system and conversation doesn’t negate the fact that some people are actually physically malfunctioning in the brain. It has happened to me three times, once with each pregnancy. And psychotherapy was a terrible part of my experience. Picture this: me with acute anxiety and depression, sitting in a group therapy session with twenty of the most miserable people I’ve ever met where I learned all the horrors that they live with — suicide attempts, cutting, rape, sexual/physical/emotional/drug abuse, irrational fears, etc. Then I got out of the hospital and proceeded to therapy with my husband where I sat for an hour while my husband told the therapist everything that was wrong with me and reviewed the most tramatic events of my past (over-achiever, over-thinker, my dad’s a perfectionist, my parents fight a lot, my sister drowned, I miscarried, etc.) under the premise that they could figure out what was causing my anxiety/depression. When in reality, anyone WITHOUT mental illness would have left that session feeling depressed. Not exactly what I needed at the time, to say the least. Then the Zoloft started working and the nightmare ended.

          Misunderstandings about mental illness are perpetuated by people who do not actually have mental illness and then are “cured” by time/friends/thinking as well as by people who have real issues they should work out but choose to cover them up with SSRIs (like my friend who hates her husband so takes Zoloft to make living with him less emotionally taxing).

          But the fact remains that mental illness is a medical problem, and SSRIs can be very helpful for some people. “SSRIs have no clinically meaningful advantage over placebo” is an eroneous conclusion to draw from the data presented. People take SSRIs because they work. If they don’t work for that person, they switch to a different drug or try another therapy. The fact that sales of SSRIs is so high disproves the author’s conclusion.

  2. The premise about medicating a psychological and social problem is dangerous. Forget the studies and “results” with SSRIs and other psychotropic drugs, or even with natural supplements.

    To label the issue as medical, genetic, and/or biological does a few things:
    1) It further supports the idea of learned helplessness. (Likely already an issue with the person; don’t make it worse for him, guys!)
    2) It removes personal responsibility for how one responds to their feelings; the opposite of empowering someone.
    3) It gets adults and parents off the hook for the effects of child-rearing. Rather than looking in the mirror and putting our children’s mental health first, it’s easier for us to label and medicate them. Parents have near full control of their child’s environment; the biggest decision was… having a child in the first place. The parent, not the child, must take responsibility for the environmental and nurturing factors that affect the child’s brain development. Period.

    Sure, there’s the conflict of interest with psychiatrists and pharmaceutical businesses. Sure, there’s the financial incentive to continue medication. But guys, that’s not nearly as important as the premise itself, which I’ve explained above.

  3. I would call a 27% success rate as being clinically meaningful. I am one of those people who became depressed in my early 20s to the point of crying and sobbing several times a day for months on end, and when I began a very common SSRI medication, all symptoms ceased thereafter. I have been using this SSRI for years at a very, very low dose (one fourth the normal amount) successfully and without any side effects. When I go any lower on it, or when I forget to use it on some days, I notice some depression and anxiety symptoms coming back.

    This SSRI medication works on me and I have no side effects. I disagree with your article.

    • Why don’t you think that all the better feelings could be through the placebo effect rather than the medication doing anything? They have shown that placebos are as effective as ssris, but if you flip that around, that means ssris are shown to do nothing, and simply the effect of putting the pill in your mouth is what is causing the improvement. The reason you feel worse when you lower your dose or forget to take it, it because you KNOW you have done this.

  4. I wish there was a edit button, I see several spelling and grammar mistakes. My Dyslexia at work! It looked fine the first two times I read it. Thanks!

  5. 5HTP works for depression and the studies have shown that it works better than the placebo.  I agree SSRI’s are dangerous. However, I have found 5HTP and Gabba work better than therapy.  What do you think of Dr Amen’s work re the brain , his MRI’s showing there is a difference in the way a healthy brain and a brain with a chemical imbalance lights up. A friend has a 7 year old child. At 5 she tried to kill herself. She was first DX Bi-Polar and now they tell her mother she has schizophrenia. She was adopted at birth, a biological mom was a drug addict. Her new family is educated, loving and wonderful. There is something wrong with her brain, and therapy did nothing to help her. However, I wish her mom would believe in alternative therapies and take her to Dr Amen who one of the other Dr’s using more natural methods. She is such a beautiful child it is heart breaking.

  6. I have found this personally to be the case; almost immediately after I took an SSRI my symptoms began to abate.  I have friends who take an SSRI a few days before their period then stop (not recommended by their MDs)…