Serotonin Syndrome Too Much of a Good Thing Part 2/3

February 22, 20140 Comments

In part two we’ll pick up where we left off trying to determine what causes depression followed by some lesser known, yet very dangerous, side effects of serotonergic drugs.

In the depressed patient nobody really knows what’s happening in the brain itself. Currently, there is no solid theory that everyone agrees on either. Recently some authorities have been suggesting that inflammation is the cause of depression and perhpas other psychiatric diseases. They have a lot of animal and human research to back it up. I tend to agree with this because the incidence of inflammatory diseases and depression is going up even when we factor in Big Pharma’s aggressive sales. We also see that many inflammatory diseases like diabetes have higher rates of depression. An interesting point Dr Blaylock makes is the fact that over the last 30 years our food supplies have become riddled with ever increasing amounts of excitotoxins like MSG, NutraSweet and HVP among hundreds of others. Are you familiar with excitotoxins? If you doubt it look at the gum section, try to find one brand of chewing gum that doesn’t have NutraSweet in it. The FDA’s position is that they are harmless. They provide no upper limit for the amount that you can put into foods. But we know better don’t we?

These compounds are powerful excitotoxins that can cause brain inflammation especially when combined with any number of dangerous drugs or environmental toxins like vaccines, pesticides, or aluminum. In the book I get into how these toxins combine synergistically in my section on Dangerous and Deadly Dysergies, a DADD if you will-but will you? (For a detailed description you’ll have to wait for a blog or the book)

Here’s how it might play out in depression: It turns out that inflammation causes your brain to secrete more glutamate. This alone is not healthy because the brain glutamate pathways are numerous. They help control levels of serotonin and dopamine in other brain regions. Glutamate on its own can further brain inflammation since glutamate, even as a neurotransmitter, is an excitotoxin when it is not carefully regulated in the brain. Within the brain, inflammation causes a certain enzyme to increase in activity. This enzyme converts serotonin into a very potent neurootoxin called quinolinic acid. Now imagine if you are on an SSRI which keeps your brain supplied with an abundance of serotonin, and you have silent inflammation which is as common as falling off your roof cleaning gutters. This helps explain the new disease tardive dysphoria (TD) seen with chronic antidepressant use. TD is a permanent depressive state that develops from chronic SSRI use. It may be caused by the above mechanism leading to excess levels of quinolinic acid.

As you can see it’s quite easy for the typical American to further brain inflammation nowadays. This may be the explanation for depression we are looking for since inflammation causes so much human misery already it’s not the least bit surprising that it can also cause depression and anxiety. An anti-inflammatory lifestyle (proper food, sunlight, exercise) cures most forms of depression especially the type that’s difficult to treat with medications. Perhaps science will show that there are inflammatory conditions that directly cause depression.

Conversely, many authorities do not buy into the camp that there is a physical disorder for any mental disease. They insist that depression is simply an emotional reaction to sad life events; it’s perfectly plausible when we realize that so far after millions of dollars of research to find a physical cause-such as a CT image-of depression we are no closer than we were in the 50’s. This is also true for other psychiatric diseases such as schizophrenia. Only time will tell for sure. For now we do have evidence that some “psychiatric diseases” (really brain disorders) have physical roots. Look at any toxic delirium for example and serotonin syndrome as you will see, is one of those. But that does not mean that we will ever find a physical cause in such mundane disorders as depression or generalized anxiety disorder.

Are these drugs any good at treating depression? By sales alone you would think they are miracle drugs. If you look at all of the people taking them you might conclude that they must work right? As it turns out they do in fact help treat depression but the funny thing is almost any drug will effectively treat depression if approached correctly. What I mean to say is that SSRI’s work no better than a placebo. You heard right, no better than a sugar pill or any number of about 12 other selected drugs (atropine, phenobarbital, etc) that have no psychiatric indications. In fact, with the proper experimental setup you could use virtually any drug to treat depression and get about the same results. It’s already been done; think about that for a moment. For example, when a patient is given an active placebo, one that is designed to have some side effects like dry mouth, patients respond as well or better than with an SSRI.

Do they hurt people? Yes, affirmative, SS is one of many. See below for a list of some of the newer findings on these drugs. You might be shocked at how dangerous these chemicals are. Do they help people? Yes, but that’s not to say that a sugar pill or an active placebo wouldn’t work just as well. How do they work at treating depression? That’s a good one since the theories of how depression works on a molecular level are all obsolete; it appears that as we pull back the curtain on this elaborate hoax it’s just a placebo effect and nothing more.

What do they actually do? Besides increasing available serotonin, they do many strange things to the psyche; they are very powerful mood altering drugs but if you want to know if they powerfully cure let’s say, anxious depression into something more tolerable, the answer to that is generally no. Often times the tradeoff for placebo level treatment, and suffering from the numerous harmful effects from these drugs is not worth it. For example, you wouldn’t want to trade anxious depression for mania and homicide would you? True, only a small percentage become manic but even at 6% out of 50 million people that’s a lot of maniacs out there. Why bother when exercise and psychotherapy are harmless and work better than pills.

Unless you think poor Jimmy’s “side effects” were an acceptable tradeoff treating his anxiety and supposed depression. (Refer to the case of poor Jimmy in a series of previous blogs on, where his drugs scarcely placated the anxiety he had only to give him a heart attack, sudden death (resuscitated), diabetes, obesity, chronically impaired brain function, and ultimately landing him in the OR for an emergency craniotomy all directly the result of these drugs).

In summary, I have pointed out to you that the new classes of antidepressants such as those listed above and several herbs as well are serotonergic. But that’s about all we know. We cannot say they treat depression any better than placebo because number one: Dr Irving Kirsch has proven it in his book The Emperor’s New Clothes that the SSRI class of antidepressants work no better than placebo, and number two: we do not have a theory or a model of depression that has survived scrutiny, and three: we are far from having the technology to actually measure synaptic brain serotonin or any other neurotransmitter. We can only measure metabolites of serotonin in the CSF, blood or urine. As many as 25% of our population is taking one of these, and they have terrible side effects such as mania. Since there are better ways to treat depression, and since these drugs simply do not work, we need to be cautious about who takes one of these. These are not harmless medications.

There are two situations where the patient’s life may be threatened. One is with abrupt withdrawal and the other is SS. Next week we’ll discuss the signs and symptoms of serotonin syndrome (SS) and how to treat it using both acupuncture and western medical advice.

For the interested reader pick up Dr Peter Breggin’s recent work called Medication Madness. This is an Alice in Wonderland description of the horrors and fascination with these bizarre chemicals. After you read this book you will never opt for an antidepressant.

In addition to the standard issue side effects that you probably know like headache and nausea there are other less known but more important problems associated with taking these drugs chronically. You should keep a copy handy for reference.

  1. Recently the fad has been to prescribe an antidepressant along with aspirin (ASA) to post-infarct (heart attack) patients. If you mix ASA with an SSRI you increase your risk of bleeding by 42% (The Pulse).
  2. Research presented in 2011 at a New Orleans meeting of the American College of Cardiology shows that antidepressants may actually accelerate atherosclerosis by thickening arterial walls.
  3. Literature review of studies from 2000-2007, published in Expert Opinion on Drug Safety in 2008 found that “Antipsychotics can increase cardiac risk even at low doses, whereas antidepressants do it generally at high doses or in the setting of drug combinations.”
  4. In a 2009 study antipsychotic drugs doubled the risk of sudden cardiac death. Mortality was found to be dose-dependent, so those taking higher doses were at increased risk of a lethal cardiac event.
  5. A new article published in 2013 in the prestigious British Medical Journal (BMJ) showed that several antidepressants including Celexa and Lexapro caused dangerous changes in the electrical activity in the heart which could lead to a fatal rhythm disturbance and sudden death.[1]  The study involved over 38,000 patients where it was found that one in five developed Q T prolongation while on these drugs which can lead to a deadly condition called Torsade de Pointes, a fatal form of ventricular tachycardia, which can be precipitated in patients at risk for low potassium and magnesium. I should note that nearly 70% of the population is already magnesium deficient.
  6. Suicidal ideation and violent behavior. As Dr Breggin mentions teenagers and young adults are at increased risk for suicide. In some kids SSRI’s create a dream-like state (mania) but more on par with a nightmare-that is hard to tell from waking reality. These children and some adults are then capable of the most monstrous acts of violence while in this soporific repose. The most at-risk time is when dosages of antidepressants (or atypical antipsychotics-AAP) are changed-usually when increased. During that acceleration period psychotic breaks can occur but they have also caused mayhem when suddenly decreasing the dose as well.
  7. All of the newer classes of drugs as well as the TCA’s increase your risk for diabetes. The atypicals (AAP) also promote metabolic syndrome which is characterized by low HDL, high triglycerides, beer belly or visceral obesity, hypertension, insulin resistance (a pre-diabetic condition) and eventually heart disease and diabetes for many. If you are on both, which is a very popular answer to failed monotherapy for depression, your chances of developing diabetes is profoundly increased.
  8. Risk for stroke may be as high as 45% higher while on an antidepressant.[2] The research also found that overall death rates were 32 percent higher in women on the drugs.
  9. Fetal toxicity and Stillbirth-doubles you chances of stillbirth.
  10. SSRI’s recently found to increase the risk of serious heart defects in newborns.[3]
  11. Newborns born to mothers taking SSRI antidepressants have a greater chance of developing persistent pulmonary hypertension an incurable condition.[4]
  12. Some are teratogenic leading to a 40% increase in cleft palate and other birth defects.
  13. Immunity-since serotonin is located throughout your body, not just in your brain, it interferes with immune cell signaling and T cell function.
  14. Osteoporosis-women on antidepressants had a 30% higher risk for spinal fracture and a 20% over higher risk for other fractures.
  15. Death-death rates 32% higher in women on antidepressants.
  16. Serotonin syndrome. The serotonin syndrome is a hyperserotonergic state which is a very dangerous and a potentially fatal side effect of serotonergic enhancing drugs which can have multiple psychiatric and non-psychiatric symptoms. It is a condition which has been on the rise since the 1960′s when we began using more and more drugs which directly affect serotonin. This is a toxic condition which requires heightened clinical awareness in order to prevent, recognize, and treat the condition promptly. Promptness is vital because, as we just mentioned, the serotonin syndrome can be fatal and death from this side effect can come very rapidly….The suspected cause of that increase is the introduction of the new selective serotonergic enhancing agents in clinical practice – the SSRIs. This disorder, brought on by excessive levels of serotonin, is difficult to distinguish from the neuroleptic malignant syndrome because the symptoms are so similar. The neuroleptic malignant syndrome is a serious condition brought on by the use of the neuroleptic (antipsychotic) drugs.
  17. The Serotonin Syndrome
    Prominent SSx's of SS.

    Prominent SSx’s of SS.

    N Engl J Med 2005;352:1112-20.Clinical triad of the serotonin syndrome:

    1. Mental-status changes

      agitation and delirium

    2. Autonomic hyperactivity

      tachycardia, mydriasis, diaphoresis, the presence of bowel sounds and diarrhea

    3. Neuromuscular abnormalities

      Hyperreflexia, inducible clonus, myoclonus, ocular clonus, spontaneous clonus, peripheral hypertonicity, and shivering

[1] BMJ. 2013 Jan 29;346:f288. doi: 10.1136/bmj.f288.

[2] Arch Intern Med. 2009;169(22):2128-2139. doi:10.1001/archinternmed.2009.436

[3] Malm, Heli MD Selective Serotonin Reuptake Inhibitors and Risk for Major Congenital Anomalies

Obstetrics & Gynecology: July 2011 – Volume 118 – Issue 1 – pp 111-120

doi: 10.1097/AOG.0b013e318220edcc. ( 05/31/2012

Filed in: OFFICE EMERGENCIESSerotonin Syndrome
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About the Author ()

Christopher Rasmussen MD, MS is Founder and Professor at AdaptiveTCM where helps Traditional Chinese Medicine Practitioners treat complex patients with confidence through providing online CEUs and research. Dr. Rasmussen is currently writing a comprehensive, preventive medicine book, with an emphasis on inflammatory components of disease prevalent in today's patients.

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