The People's Perspective on Medicine

Show 890: Do Antidepressants Really Work?

Antidepressants are not as effective as they have been portrayed, but other approaches can help alleviate depression.

For more than two decades, antidepressants like Prozac, Zoloft, Paxil or Effexor have become household names. They are widely used to treat the most common mental illness. But do they really work as well as most of us think? This question is being briskly debated by medical professionals, as the point-counterpoint in BMJ (Jan. 22, 2013) demonstrates.

Drugs Are Not Always More Effective Than Placebo

Research studies show that these SSRI drugs don’t always work better than the inert sugar pills they are tested against. But that doesn’t mean there is no hope for people with depression. Several non-drug approaches are at least as effective as antidepressants. Knowing how to evaluate the benefits and risks of SSRI medications can help patients make good decisions in partnership with their physicians.


Irving Kirsch, PhD, is Associate Director of the Program in Placebo Studies at the Harvard Medical School, lecturer in medicine at Beth Israel Deaconess Medical Center, Professor of Psychology at the University of Plymouth (UK), and Professor Emeritus at the University of Hull and the University of Connecticut. His book is The Emperor’s New Drugs: Exploding the Antidepressant Myth. The photo is of Dr. Kirsch.

Erick Turner, MD, is Assistant Professor, Department of Psychiatry and Department of Pharmacology, Oregon Health and Science University (OHSU), Portland OR.

Stephen Ilardi, PhD, is associate professor of clinical psychology at the University of Kansas and author of The Depression Cure. His website is

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.” .
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One of the audio files for program 890 suggested that 1000-2000 mg of EPA is a therapeutic dose, I visited the local chain drug store and saw several brands of tablets 1200 mg fish. From the bottle labels only 300-360 mg of EPA is contained in each dose. Thus, the recommended amount EPA requires 3-5 doses daily. Is taking this much safe ?
PEOPLE’S PHARMACY RESPONSE: Five doses daily could interact with aspirin or other anticoagulants to cause excessive bleeding; it’s possible that susceptible people would find bruising or bleeding more common just on that much fish oil alone. If you can find a brand that has more EPA (not easy) that might be better.

When I moved into perimenopause (my menopausal period lasted 10 solid years) I began to suffer from depression so severe that some days I would just sit and weep, feeling that life was utterly pointless. When I wasn’t weeping I was having crippling anxiety attacks. I could barely work or communicate with others.
My doctor tried a few different antidepressants, but nothing helped. The best effect I achieved on the drugs was to feel emotionally numb. I felt like a zombie. Lexapro was the worst; within three days of starting Lexapro not only was I anorgasmic, but I found myself sitting on my porch steps actively imagining effective ways to kill myself–and planning how to get the necessary equipment to carry out the plan!
St. John’s Wort was effective but I developed such extreme photo-sensitivity that I felt like a vampire on the beach in Hawaii. Kava kava worked like a charm, but I felt I had to take Milk Thistle to support healthy liver function–and I had to take increasingly larger does to maintain the positive mood state.
Finally I found a doctor who specialized in bio-identical hormones who tested me for the usual markers in post-menopausal women — estrogen, progesterone, thyroid, etc.– and although my levels were ‘within the normal range,’ he considered the symptoms I was reporting (extreme hair loss, aching joints, coarsening of skin, brittle nails, fatigue, frequent anxiety attacks, extreme depression) and put me on low-dose Armour thyroid supplements, estrogen, progesterone, but most importantly, he inserted a very low dose TESTOSTERONE implant in my hip!
I woke up the next day feeling focused and optimistic for the first time in ten YEARS! I couldn’t believe the difference in my mood! My doctor was pleased with my response, saying that in his practice he’s noticed that a lot of women benefit from adding testosterone to the hormonal balancing act. He also mentioned that he’s seeing more men whose testosterone levels were well below optimal and who suffer from fatigue and depression because of it.
Oh, and after six months, I haven’t noticed a single side-effect. I guess the dose isn’t high enough to cause facial hair, aggressive mood state, deepened voice or any of the things you think of when you think ‘testosterone.’ I just feel normal again. It’s wonderful!

Lucy, I just have to write to give you a thumbs up, a hug, a thank you! You make a great point and a powerful reminder.
I will smile more broadly when greeting and even when walking by people today. Will make more of an effort.
Didn’t Dale Carnegie say think positive and you will be positive… or something like that? Perhaps it also works if we act happy, after awhile we will be happy. My grandfather used to sweep the sidewalk in front of a department store. He lived until he was 98 years old, never hospitalized, and I remember him laughing and smiling all the time. I know his life was not an easy one, but he was always cheerful. I am sure there are serious ailments that must be treated with medications, but we can all try to smile. Thank you Lucy!

In my late thirty I started slipping into mild to moderate depression. I wrote it up to job dis-satisfaction and the economy. I was also irritable and sleeping poorly. I didn’t see a psychiatrist or seek anti-depressants figuring I would muddle through. In my 40s my doctor ran a series of blood tests, including checking my testosterone.
The tests showed that I had the testosterone levels of an 80 year old. My doctor put me on testosterone injections and in not time I felt like my old self. The change was so great that some co-workers thought I was on anti-depressants. Many of my friends have started testosterone replacement therapy and have seen the same results.
I sometimes wonder what would have happened if I had sought some psychiatric help and been put on some sort of SSRI, when the problem was hormonal and easily solved.
I know this doesn’t apply to a lot of people, but it is worth noting that the problem can be better solved by looking at other avenues.

One pill of Zoloft caused me such negative effects that without my wife I would have died. That was a single pill. I was not suicidal before or after. Paxil made me emotionally numb, sexually dead. Effexor took six months to taperoff and i vomited daily and was dizzy for another six months. Also there are tests for which drug will work, Japan uses them for everybody

Why does nobody talk about HERBS as antidepressants?
Once in a while, when my world looks grey, I take a supplement. I take one only (not two as the instructions say) and it helps every time. After an hour or so, my world is not grey anymore. The ingredients are Kava Kava, Passionflower, St.John’s Wort and some others.
For example,
We don’t recommend kava kava, although it has excellent anti-anxiety activity. Some forms of this herb can harm the liver, and the US market does not have adequate protections against that.

I personally have been on Prozac and then Effexor XR more recently for approx. 10 years and found both to be helpful when combined with talk therapy with a psychologist. Frankly I am not good about exercising and that certainly could prove to help my depression also, but I am pretty certain I have a biologic predisposition to some amount of depression from my mother’s side and some untreated predisposition for anxiety from my father’s side. Therefore, I have made peace with the fact that I could likely be involved in some form of treatment for the rest of my life.
The medication and therapy combo has worked well for me, and once I complete graduate school (I have been working full time all the way through and going to class at night) I plan to attempt to ‘dial back’ my medication and see how I feel once some significant stress has been alleviated when I graduate in Dec 2013.
I would prefer not to take medication if possible because it has definitely affected my sex drive negatively. I have some interest, but certainly not the interest I think I would normally have if I were not on the medication. I am engaged and have been in a relationship with my fiancee for 3 years.
Thank you for the story today on the radio, it was interesting information and perspective.

I was given Prozac the first time in 1983. Every one around me noticed an immediate improvement in my mood although I didn’t notice it. I have been on anti-depressants since then and about 7 years ago my medication was changed to Effexor XR and I am still taking that. The Prozac had sexual side effects – no interest. The Effexor has perked up my libido.

How many of these depressed people are feeling terrible because they are not being treated kindly by others? Apparently in India and China there are many suicides among women who are having horrible family troubles, primarily an unkind husband or mother-in-law. Maybe we could all play a part in helping people in our lives not get depressed, simply by being warm and caring and loving to them.
If each of us woke up in the morning and were kind and cheerful to our spouse at the breakfast table, the clerks at the market, our coworkers at the office, our children, strangers passed briefly on the sidewalk (just a friendly smile and “good morning”) there might be less depression. Mild depression can be catching, the way the flu is. We are told again and again to wash our hands and get flu shots, not only for our own health but to stop us from passing illness on to others, especially the vulnerable.
Kind words, smiles, little gestures of friendship can make all the difference to a vulnerable person. Bad moods should not be passed around.

Dr Kirsch hit the nail on the head when he said “We really don’t know.” He should have stopped with just that. As good as our knowledge is, we really don’t know much about how and why most drugs work. Or why they work in some people some times and not others. Or why they sometimes cause side effects.
Modern science does accept that individuals are unique and each person’s circumstances are often unique. But we don’t properly accept that there are many more variables than we can control for in testing. Unfortunately, we go on continuing to expect that a tested treatment will work for most of us. It usually doesn’t.
Dr Kirsch may believe that antidepressants work no better than placebos. But, nobody knows that for sure. For some people they do work.

I appreciate your balanced presentation of ongoing debates of the efficacy of antidepressants. I’ve resisted providing a testimonial, but my experience convinced me that, coupled with non-medical psychotherapy, Paxil helped me overcome a deep long term (6 year) depression that had proved resistant during 3 years of psychotherapy alone.
I did experience side effects – difficulty achieving orgasm, rococo dreams and late in the 6 month course of treatment uncontrollable yawning. When the yawning began, my psychotherapist told me it was time to begin to end the treatment, and she gave me instructions to taper off of the drug over several weeks. Paxil, weakly psychotherapy and behavioral interventions finally succeeded in breaking the cycle of depression I had been in for many years. The illness didn’t render me nonfunctional but severely affected my relationship with my parents, my spouse and my children.
The presentation indicating that the drugs have some effect (a difference in positive outcomes from 50% of patients to 60% of patients is a 20% improvement after all) is consistent with my experience. Dr. Kirsch’s critique is useful in countering what’s become significant overuse of these drugs as stand alone treatment for depression. But used appropriately as I believe my therapist used them helped me overcome an increasingly severe mental illness 15 years ago.

Dr Kirsch has good points but is markedly biased against medication. Talk therapy that he recommends is NO BETTER THAN PLACEBO for shortening duration of depression

Hurrah for healthy eating!
Processed foods and sugars send my blood sugar on a roller coaster ride. My brain function becomes sub optimal causing waves of confusion, adrenaline induced anxiety and then severe lethargy. All of this changes my behavior and mood.
Before I understood my food consumption was to blame, I accepted these behaviors and moods as part of who I was. This was a strong contributor to my depression.
I now enjoy the mood stability that comes with healthy eating. Joe and Terry promote healthy eating and stable blood sugar on this show, which is one of the many reasons I continue to tune in.

my god what a pleasure it is to hear a topic, any topic, discussed with the rational intelligence that y’all bring to your show. your show is truly unique. the problem is, tomorrow i’ll listen to the sunday morning blab-a-thons and get depressed all over again.

I was under a lot of stress at work. Was unable to get outside and find time and the desire to exercise and eat properly. I gained weight, so slowly it was imperceptible to me while it was happening, but the scale showed it and I kept buying bigger clothes. My blood sugar was going up every year. Finally, I cried a lot.
My friend referred me to a wonderful psychiatrist. The doctor prescribed a variety of anti-depressants and wrote a note to disable me from work. I started taking yoga classes, sat in the sun, walked every day, ate carefully, whole foods like dark green leafy things, reds and oranges and all kinds of vegetables and fruits, with some fish and minimal chicken.
Slowly the weight came off. My blood sugar is down. I no longer have high blood pressure (was on bp meds for many years). I was on and off the medication as quickly as possible, taking low dose for only a few months. When I took the prescriptions my arms and legs felt heavy and I felt like I was in a fog with no interest in doing anything.
While I think there may be some who need medicine, I hope people try to exercise every single day (go outside and walk, join a community exercise class, clean house, scrub floors…) and eat whole foods that have not been tampered with by others (restaurants add too much fat, sugar and salt and same for processed foods). My hope is for everyone to feel as good and happy as I do today.
The psychiatrist was a blessing. She enabled me to take time to take care of myself. I don’t believe the prescriptions helped. When I eat unprocessed food I feel so much better the next day. When I go to an exercise class, walk or cleaned my house, within 30 minutes my spirits lift and I feel much better than when I started.
It doesn’t have to cost anything to live this way. I feel like I save money by building immunity and not getting sick.

I’m a long time listener. The ranges of views expressed are important. It allows us to consider alternate methods for staying healthy and addressing disease.
I didn’t hear the medical doctors speak but I did hear Dr. Kirsch speak. It sounds like he is an authority on non-drug approaches to abate depression. But he demonstrated a lack of concern for human life when he discussed his views on pharmacological treatment of depression. The efficacy of antidepressants relies on the intelligence and experience of the doctor prescribing it. What Dr. Hirsch did not discuss are the effective ways to prescribe antidepressants. I propose that the majority of antidepressants are prescribed by non-psychiatric doctors who form his statistics.
I was diagnosed with bipolar depressions in 1987 after a failed suicide attempt. The suicide was planned over several weeks, the execution was meticulous and I sent letters to my family.
I am SO grateful for that failure. I now truly love life and I have enriched the lives of my associations and friends. There is a line in “It’s a Wonderful Life” I will never forget, “no man is a failure who has friends.”
My psychiatrist had decades of experience, was well studied on all the drugs he prescribe, understood the effects of brain chemistry, mood, and side effects. He knew this from literature, but more importantly, he knew this from experience with thousands of patients. He was a confident, bold, gregarious doctor, but never was he reckless.
Over the course of several years, we tried several drugs that each had some benefit. He was able to fine tune a “cocktail”, combination and dosage, of antidepressants that keep me alive. I know the meds work because last year, I decided to stop my meds, just because I thought I could be healthier med free. I became manic, took on way too many responsibilities in and outside work and cut my sleep way back. After pulling an all-nighter, and sleeping only 2 hours, I woke up one morning feeling that my responsibilities were impossible to bear, I felt hopeless, and felt suicide was my only option. I know what suicidal intent feels like, and that’s what it was.
What I did was I prayed for help. Around 7 am, I called two good friends who understood bipolar disease, and with great compassion, we worked out a solution and safety mechanisms to keep me hopeful. The major solution was to stay on my medication for the rest of my life.
Since 1989, I developed this process that works for me. Bipolar disease is always ready and willing to destroy me. I declared war on my disease. I’m an engineer, and I still work full time, but work has become a means for life, and not my life. I developed my faith, I pray regularly, I read the bible, I practice yoga, use cognitive behavioral therapy, joined many social groups, developed friendships, I own dogs, I avoid toxic people, I seek out nurturing people, I renewed my bonds with my parents and siblings, I compete in triathlons, I’m learning piano (again) and steel drums, I developed landscaping as a hobby, I tinker with technology, I’m a Toastmaster, I and my dogs compete in a sport, I’m reading fiction and nonfiction again, I support over 10 non-profit enterprises and endeavors with sweat equity and money, I am on a never ending journey of self-improvement.
Most importantly, I continue my drug regimen of lithium, Luvox and Wellbutrin. As a side note, when I meditate, I can see waves of dopamine develop then swirl in blue receptors of my optic nerve. I thank the Wellbutrin for this – very cool.

The allegations presented in this show are disturbing and compelling.
If these charges prove to be true, this establishes that the pharmaceutical companies have mastered the techniques of manipulating the approval processes of the US Food and Drug Administration to gain approval for drugs which might be less effective than existing drugs or even dangerous.
This is a paradigm shift for US healthcare, which is so incredibly costly that it threatens the solvency of the United States.
In my opinion, People’s Pharmacy is a pillar in the movement to control quality and costs in our out-of-control healthcare infrastructure. The US has healthcare costs double that of any other industrialized country, yet outcomes are markedly inferior to many other countries.
The newborn morbidity rate of Cuba is superior to that of the US, as an
example of our pervasive mismanagement of healthcare.
A recent Forbes Magazine lauded Joe and Terry Graeden for their dogged pursuit of reports from listeners of problems with one generic drug, which
was found to be defective and was taken off the market by the FDA.

Good radio show this morning.I have had a mild depression since last May, was on Zoloft for awhile, which did help a little, but no longer are taking anything for depression. I joined a line dance group at the senior center and it helped the most.

Wanted to share an off label use of antidepressants: I had a total hysterectomy 2 years ago. All went well including working with a compounding pharmacist on HRT except for the hot flashes that continued to interrupt sleep.
My family nurse practitioner suggested putting me on Zoloft. I was offended because I did not feel I had any signs of depression! She agreed but shared with me the use of antidepressants in helping hot flashes.
I am a nurse that has always searched out the clinical reason behind why we do things. After finding information confirming its use, I agreed to try it. To my surprise, the hot flashes quickly subsided!
I tried weaning off the Zoloft but found that within 24 hours, the hot flashes returned. I noticed no change in my mood which made sense since that was not my diagnosis. So, I am back on the lowest dose of Zoloft.
I have shared this information with a friend who has been suffering from hot flashes and it’s sequela for over 15 years. She has a cardiac history in her family so she can’t use HRT. Her doctor tried her on an antidepressant and she started to sleep through the night for the first time in years!
We are both avid gardeners so that is our natural mood therapy!

Has anyone talked about Transcranial Magnetic Therapy for depression and mood?
Thank you,

The show has talked about those who have depression — what about those who have been prescribed SSRIs for OCD?

I’ve been taking Wellbutrin xl 150 mg for two years. I think it is working well. I suffer from depression and seasonal effective disorder.
The past four months have been difficult, even with a light box, and I considered upping the dosage, but didn’t. Now that there’s more light, I’m feeling a lessening of the “pressure.” Also, I’ve started taking a painting class and that is doing wonders.

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