“Low-serotonin doesn’t cause depression? You’re kiddin’ me, right?!”

Does low serotonin cause depression

“Just when I thought I understood my depression, and the meds that are supposed to help me manage it. And now you’re suggesting low-serotonin has nothing to do with it? You’re kiddin’ me, right?!”

It’s time we rethink what we are doing. We are taking people who are suffering from the most common forms of depression, and instead of helping them, it appears we are putting an obstacle in their path to recovery…Dr. Paul Andrews

Seems someone filled-in our friend on the gist of a recent research paper. He’s pretty frustrated, isn’t he? And who could blame him?

I mean, the theory that depression is related to low levels of serotonin in neural synapse has been pounded into our heads for decades.

And now it’s being challenged.

Thing is, though, our friend is likely upset well beyond losing a grip on what’s causing his depression. ‘Cause if the authors of the paper are correct, that SSRI he’s taking is not only doing him no good, it may be making him miserable.

Guess the mantra of psychotropic medications is biting us in the tush – “The exact mechanism of action is unknown.”

Okay, let’s slow things down and see what’s behind the hubbub.

The Science Behind Commonly Used Antidepressants Appears to Be Backwards

A team of scientists from McMaster University (Canada), led by evolutionary psychologist Dr. Paul Andrews, has published a hair-raising paper in the journal Neuroscience & Biobehavioral Reviews.

The brain-trust reviewed existing research in an effort to find evidence to support the very keystone of depression cause and treatment: depression is related to low levels of serotonin in the synapse between neurons in the brain.

What did they come up with?

Well, it’s their belief the science behind many antidepressants – particularly the SSRIs (selective serotonin reuptake inhibitors – Prozac, Lexapro, Celexa, etc.) is backwards.


A little “in case you didn’t know.” The concept behind SSRI action is keeping levels of serotonin high by blocking its re-absorption into the neurons that release it. Actually, we could include the SNRIs (serotonin norepinephrine reuptake inhibitors – Effexor, Pristiq, Cymbalta, etc.).

This is all about reuptake. For more on the dynamic, reference the article I linked to in “synapse between neurons” above.

The hard-hitting part of the paper is the belief that serotonin-boosting medications make it harder for those enduring depression to recover, especially in the short term. This from Dr. Andrews…

It’s time we rethink what we are doing. We are taking people who are suffering from the most common forms of depression, and instead of helping them, it appears we are putting an obstacle in their path to recovery.

So if this is true, why do some show mood improvement when taking an antidepressant? According to the team it’s because their brains are, in fact, overcoming the medication’s effects, as opposed to reaping its benefits.

Hmmm, so instead of providing assistance, the antidepressant appears to be interfering with the brain’s own mechanisms of recovery. Andrews supposes that could be why folks report feeling worse during their first two weeks on an antidepressant.

Why Can’t We Know for Sure, and What’s the Supposed Bottom-Line?

Why is there so much room for conjecture when it comes to serotonin’s influence upon depression? Well, according to the team, it’s impossible to measure exactly how the brain releases and uses serotonin. And that’s because there’s no safe way to measure it in a living human being.

That means scientists have to rely upon measuring serotonin levels the brain has already metabolized, and making inferences from animal studies. And that doesn’t provide the clearest picture.

All things considered, the paper states the best available evidence indicates there’s more serotonin being released and used during depressive episodes, not less.

The team goes on to suggest serotonin helps the brain adapt to depression by re-allocating its resources, giving more to conscious thought and less to areas such as growth, development, reproduction, immune function, and the stress response.

Consider this take-away. Andrews has argued in previous research that antidepressants leave patients in worse shape after they stop using them, and that most forms of depression, though painful, are natural and beneficial adaptations to stress.

Yikes! And your thoughts are?

Where Do We Go From Here?

It’s difficult writing pieces like this. I mean, news is news – knowledge is power. Yet, what about our exasperated friend? What about you? ‘Cause the paper implies that antidepressant you’re taking may be worthless, and may even be bringing you down. And that’s a kick in the gut.

Look at it this way. If Andrews and team are right, isn’t it better to cut our losses and move-on to other interventions?

Pharmaceutically, I’ve shared that other neurotransmitters, especially glutamate, may be the best point of attack for depression. Check-out the piece I wrote a while back on ketamine, which influences a glutamate receptor. And in that piece you’ll find a link to info on a glutamate influencing drug in development, GLYX-13.

And as we’re considering other depression interventions, let’s never forget the power of psychotherapy – perspective and acceptance.

But you know what? Maybe Dr. Andrews and team are flat-out wrong.

Hmmm. Right or wrong, having these discussions is a good thing, ’cause every possible angle has to be uncovered and considered if we’re to understand and effectively treat depression.

So what’s on your mind? Would you share in a comment?

  • Gilda Sanchez February 25, 2015, 2:09 am

    I think Dr. Andrews is wrong. There is another mechanism of which researchers are still trying to understand when SSRIs don’t have enough effect of some people. To claim SSRI’s are damaging rather than helping is completely overstated.
    See Dr. Andrews bio:http://www.science.mcmaster.ca/pnb/andrews/

    • npeden June 11, 2015, 9:09 pm

      geez, sorry, gilda, but i believe that both my and barcat’s experiences say that genetics should be considered. his article may be rubbish, but our lived experience is not.

  • Gilda Sanchez February 25, 2015, 2:25 am

    Dr. Andrews overstates this “SSRIs disrupt Homeostatsis” theory. Here is his article, and I think it lacks good citations: http://www.ncbi.nlm.nih.gov/pubmed/22536191

  • Chipur February 25, 2015, 9:07 am

    Thanks for the participation – with links – Gilda. You’re always the voice of well-considered reason. I’ve tapped both of the links and assure readers they’re safe. And by the way, excellent information. Openly reviewing and discussing such topics is always good. Actually, whatever it takes to keep the conversation flowing regarding cause and treatment of what we endure…

    • Gilda Sanchez February 25, 2015, 5:07 pm


  • npeden February 28, 2015, 1:24 pm

    I have been reading about this too, Bill. For me the question is true, they don’t work. But for me that is because I had a smart psych who had me tested for MTHFR and there are just about NO antidepressants I can take. Some gave me rashes and I panicked and worried about Steven Johnson’s Syndrome which can kill you (I may have the disease name wrong) and I now have permanent Tardive dyskinesia that requires daily management with amino acids for my speech to remain normal.

    So now I know why for ME, it is MTHFR. This knowledge/research you write of helps and may or may not be true, BUT I believe a deeper consideration is that these drugs cause serious, very serious side effects, as I have already mentioned. My favorite blog is Beyond Meds, where she writes of IATROGENIC damage done by psych drugs.

    A better solution may be, if you know you genetics, and you are mutated for MAO A passion flower tincture may help.

    An even BETTER solution: rewire your brain via meditation. Here is a great meditation that is easy and is said to change the brain for the better in just two weeks! I don’t think it mentions time as it does take time to do all the visualizations but if you have to, start with ten minutes. The most important step one, self love. That may be the hardest but try it out. http://m.wikihow.com/Practice-Loving-Kindness-Meditation-(Metta)

    • Chipur February 28, 2015, 4:03 pm

      Hi, Nancy! Glad you wandered on by and shared with us.

      Readers – Nancy comments frequently here on Chipur and, as she states, she tests positive for MTHFR gene mutations. The mutations don’t get the press they deserve; however, one day that may change. Because Nancy deals with it daily she knows quite a bit about it. For those who’d like to catch-up, tap the link http://mthfr.net/ Nancy also mentions Stevens-Johnson syndrome. Here’s a link to learn about it http://mthfr.net/

      Thank you for providing the meditation exercise link, Nancy. Info looks really helpful. You always share relevant and rubber-meets-the-road stuff – and it’s always appreciated…


    • BCat June 11, 2015, 5:10 pm

      I had Stevens-Johnson in 2005. I was taking DMPS to chelate high mercury per my naturopath, and apparently my elimination was not in as good a shape as it needed to be in order to excrete the mobilized mercury. After only 2 pills I started getting a black swollen rash in all my mucous membranes and then peeling. At that point it gets serious because peeling also takes place in the internal organs. People die from it in a horrible way with blackened skin all over inside and out.

      Went to the emergency room and was told ‘You do NOT want to be in a hospital with a broken skin condition’, what with skin eating bacteria and all. I was told it was either going to run it’s course and I’d get better, or I would not and there was absolutely nothing anyone could do except to offer intravenous fluids to offset dehydration. Boy, was I scared. Luckily for me, it turned around in two more weeks and I slowly got better, but with muscle aches and skin sensitivity for another 3 months. It’s most prevalent with sulfa drugs, which I’m sensitive to anyway, and DMPS is high sulfer. Thanks for the meditation, Nancy. I do much better in general when I can wind down enough to tolerate meditating. Hard during anxiety attacks.

      • npeden June 11, 2015, 6:53 pm

        Wow, BCat, you are SO lucky to be alive. Several drugs gave me rashes and I was taken of them immediately. I was very lucky.

        Interesting about the ER warning; I agree. My dad was a doc and he was the world’s most terrible patient. He used to say, “I know what they do in there”….glad you got out of there and off the heavy duty chelator. There are many that are very dangerous. Since genetic protocols all begin with fixing leaky gut, I think you need to be very careful what you put in your tummy….

        I am about to chelate but I am going to do it very slowly with chlorella which is very natural. It will probably take a long time but I am glad to be only one amalgam away.

        Hey, Bill, I made it home from scary ole San Jose. Even with my wonderful Google GPS I got lost and took several circles around. At least Google says, “turn around” or make a u turn….at least she is polite about it all.

      • Chipur June 11, 2015, 8:23 pm

        A different twist on the ’60s Dionne Warwick classic “Do You Know the Way to San Jose” (or the way back). Glad your home – safe and sound…

      • npeden June 12, 2015, 12:29 pm

        Yes, coming home was so much more easy after I got out of SJ and thank the Goddess for Google GPS…really works. HOME!

  • npeden February 28, 2015, 10:51 pm

    i am not going to comment on this research. i am going to reitrate what i said earlier: these drugs have life altering side effects during a time when any oher methods are available. i am on a ketogenic diet and my anxiety is gone. i know that is not depression. but have you even had your b12 and the form you should take tested?

    besssel von der kolk, a world leader in trauma therapy, says the dsm is of the past. health will be be determined by how well we can be in reationships. there are many alternatives to drugs, including having your genetics tested.

    please excuse my rant but i believe big pharma will klll you, not make you better.

    those of you that are doing well on antidepressants, i am glad for, but highly recommend you look at the long term effects.

    bill does an important job excoriating benzos for which i am glad. as i have high glutamate i am still addicted. pray for me that once i detox my heavy metal poisoning, this too shall pass.

    • Chipur March 1, 2015, 1:16 pm

      Thank you, Nancy. My meditations will definitely be with you.

      Readers – once again Nancy brings important information to the fore – something about which you may not be familiar. Ketogenic diet is powerful, and being utilized for much more than its original application – pediatric epilepsy. Here’s a link, check-it-out http://en.wikipedia.org/wiki/Ketogenic_diet


      • npeden March 1, 2015, 1:34 pm

        Thanks, Bill. I think it is also used with ADD kids. Maybe I said that but my main point is it has stopped my anxiety dead in its tracks. I still take magnesium twice a day and some inositol when I think to, but I am sure it is the diet. And I LOVE it: meat, vegies and lots of healthy fat. I have lost 40 lbs. btw…and my last cholesterol was down for my LDL and high for my HDL. Go figure…I am sure that this diet is not for everyone but for me it really seems to work.

      • Chipur March 1, 2015, 2:36 pm

        More great info for all who happen by. Appreciate it, Nancy…

      • steve March 2, 2015, 11:37 am

        I keep forgetting that you have this page Bill, such great information….I need to read all of this…

      • Chipur March 2, 2015, 6:03 pm

        Well, you just come on back and dig-in anytime, Steve. We’ll be here. Thanks for your visit and comment…