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вторник, 8 мая 2018 г.

The Serotonin Syndrome


Today we”ll go over two  sometimes fatal syndromes that can occur from the use of the SSRI antidepressants. The first one is called the Serotonin Syndrome which can occur when the patient experiences too much serotonin effect in the brain. The second syndrome called Serotonin Withdrawal Syndrome occurs during the exact opposite of the first when a patient misses her dose or deliberately tries to quit on her own without the proper guidance. Both can be deadly in the extreme, both can also cause mania and appalling behavior such as we have been discussing here at length in other articles. Let’s look at the first one shall we:

The symptoms of the serotonin syndrome are (from The Serotonin Syndrome, AM J PSYCHIATRY, June 1991):

1. Euphoria

2. Drowsiness

3. Sustained rapid eye movement

4. Overreaction of the reflexes

5. Rapid muscle contraction and relaxation in the ankle causing abnormal movements of the foot

6. Clumsiness

7. Restlessness

8. Feeling drunk and dizzy

9. Muscle contraction and relaxation in the jaw

10. Sweating

11. Intoxication

12. Muscle twitching

13. Rigidity

14. High body temperature

15. Mental status changes were frequent (including confusion and hypomania – a “happy drunk” state)

16. Shivering

17. Diarrhea

18. Loss of consciousness and death.

There is an additional and unique 19th symptom in which the patient experiences intense, deep, brain pain which is not like a headache either it’s a totally different type of pain.

I have made this diagnosis before and it isn’t pretty. In fact I see it as yet another form of malpractice. Why malpractice? Because it usually takes a deliberate attempt to induce this syndrome by adding in one serotonergic drug after another like you would to a lab rat. In the case where I saw it, this person (see below the case of Poor Jimmy) was slowly being driven mad. It could have easily been prevented if his psychiatrist hadn’t been so apathetic. Jimmy would describe his psychiatric appointments like this: in and out in less than five minutes. How on earth can anyone tell anything in five minutes? Every time he had a complaint (side effect) he was given another serotonergic drug. Until finally he had 5 serotonergic agents on board, five! Had I not been there I fear he would have died in the next day or two before anyone could figure out what was happening. This is the same psychiatrist that was writing for speed, amphetamine, in a patient that had already suffered sudden death but was successfully revived. Recall amphetamine has a Black Box warning that includes sudden death as a consequence of chronic amphetamine exposure.

Dr Tracy continues:

The serotonin syndrome is generally caused by a combination of two or more drugs, one of which is often a selective serotonergic medication. The drugs which we know most frequently contribute to this condition are the combining of MAOIs with Prozac (this should also include the other SSRIs) or other drugs that have a powerful effect upon serotonin, ie., clomipramine (Anafranil), trazadone (Deseryl), etc. The combination of lithium with these selective serotonergic agents has been implicated in enhancing the serotonin syndrome. The tricyclic antidepressants, lithium, MAOIs, SSRIs, ECT (electric shock treatment), tryptophan, and the serotonin agonists (fenfluramine) all enhance serotonin neurotransmission and can contribute to this syndrome. Anything which will raise the level of serotonin can bring on this hyperserotonergic condition. The optimal treatment for the serotonin syndrome is discontinuation of the offending medication or medications, offer supportive measures, and wait for the symptoms to resolve. If the offending medication is discontinued, the condition will often resolve on its own within a 24 hour period. If the medication is not discontinued the condition can progress rapidly to a more serious state and become fatal. It should be apparent that the greater the enhancement of serotonin levels, the greater the chances of producing the serotonin syndrome. Therefore it is recommended that Zoloft, Prozac, Paxil, Luvox, Serzone, etc. not be used concurrently with each other or any other serotonergic drugs and that these serious adverse reactions should be expected with these combinations (Callahan, 1993). [PROZAC: PANACEA OR PANDORA?, p. 88.]

Yet the combining of these drugs is exactly what doctors do all of the time in direct contradistinction to recommended safe prescribing methods.

Serotonin Withdrawal Syndrome (SWS) On top of that, the antidepressants produce serious withdrawal reactions, making it difficult and at times life-threatening to withdraw from them, even with the recommended clinical supervision and slow taper.


Up to 60% of SSRI treated patients will have some form of serotonin withdrawal syndrome if they abruptly stop their antidepressant. There are five core systems affected:

I.            Dysequilibrium leading to ataxia (unable to walk a straight line)

II.            GI symptoms such as nausea and vomiting, or diarrhea

III.            Flu like symptoms

IV.           Sensory disturbances such as electrical shocks, and paresthesias

V.            Sleep disturbances such as insomnia and vivid dreams

The psychological symptoms include anxiety, agitation, crying spells, irritability. The afflicted patient may experience the feeling of “going postal” wanting to jump out of a car at 80 mph.
FINISH Mnemonic for Recognition of Antidepressant Discontinuation Syndrome[1]

Flu-like symptoms
Fatigue
Lethargy
General malaise
Muscle aches/headaches
Diarrhea
Insomnia
Nausea
Imbalance
Gait instability
Dizziness/lightheadedness
Vertigo
Sensory disturbances
Paresthesia
“Electric shock” sensations
Visual disturbance
Hyperarousal
Anxiety
Agitation
Keep in mind that withdrawal is not to be taken lightly as patients can die from this or have a psychotic break such as full blown mania. Dr Tracy provides a CD on her website titled Help I can’t Get Off My Antidepressant for any patient or physician interested in learning a way to wean yourself off of these powerfully addicting psychotropics.

Dr Breggin just published a book devoted to weaning one off of these mind melding materials: Psychiatric Drug Withdrawal: A Guide for Prescribers, Therapists, Patients and their Families by Peter Roger Breggin (Jul 19, 2012)

Recently a study came out (2011) that confirmed how difficult to near impossible it is to conventionally stop taking an antidepressant. The result of the study, Published in the journal, Frontiers of Evolutionary Psychology, was expressed by the lead author, Paul W. Andrews in Science Daily:

“We found that the more these drugs affect serotonin and other neurotransmitters in your brain—and that’s what they’re supposed to do—the greater your risk of relapse once you stop taking them…Our results suggest that when you try to go off the drugs, depression will bounce back. This can leave people stuck in a cycle where they need to keep taking anti-depressants to prevent a return of symptoms.”

I received this information from Dr Ann Blake Tracy’s newsletter. It only confirms what we already know. The only way to be rid of these drugs is to slowly, and I mean slowly, reduce your dose over 6 months or more. Of course, when you break through and develop anxiety or depression from weaning too fast your psychiatric Doc in the Box (P-DIB) will automatically conclude that it is your native disease that’s manifesting and give you another SSRI or up your original dose.





[1] Christopher H. Warner  Antidepressant Discontinuation Syndrome Am Fam Physician. 2006 Aug 1;74(3):449-456. (http://www.aafp.org/afp/2006/0801/p449.html) 04/30/2012

PSYCHOPHARMACOLOGY

VENN-DIAGRAM OF PSYCHOACTIVE DRUGS


Psychopharmacology a term first coined in the early 20th century is the term used to describe the science of psychiatric medications.
The timeline for psychopharmacology and its antidepressant/antipsychotic drugs are as follows:[1] For completeness I have added in a few key items in brackets.
The 1950’s
  1. Development of phenothiazines [E.g., Thorazine]
  2. Discovery of iproniazid’s and Monoamine oxidase inhibitors (MAOIs’) antidepressant effects in tuberculosis patients
  3. Synthesis and beginning use of  Tricyclic antidepressants (TCAs), like imipramine, for depression
The 1960’s
  1. Beginnings of broad clinical use of TCAs, like amitriptyline-Elavil, now preferred over MAOIs
  2. [Ritalin approved for kids]
  3. Catecholamine hypothesis of depression widely discussed and investigated
Up to the early1990’s
  1. Development and clinical use of SSRIs, like fluoxetine, citalopram, and sertraline
  2. Broadening use of antidepressants for other conditions like anxiety disorders and painful conditions
  3. More common prescribing of antidepressant agents by primary care physicians
Up to the present day
  1. Synthesis and clinical use of dual-acting norepinephrine and serotonin (NE and 5-HT) antidepressants, with fewer TCA-like side effects, including SNRIs (venlafaxine- Effexor, duloxetine-Cymbalta), mirtazapine-Remeron, bupropion, and nefazodone
  2. More rigorous investigation of the analgesic properties of newer antidepressant agents
  3. [The widespread use of the atypical antipsychotics characterized by their dual action of blocking both dopamine and serotonin receptors (D2, 5HT2) such as Seroquel]  
Below is a listing of all the currently available atypicals (AAP’s) on the market.
I listed many of the atypicals along with their names off Wikipedia. Several of the atypicals are worse for causing weight gain.[2] W+ indicates those associated with the greatest risk of clinically significant weight gain. ὡ indicates moderate risk of weight gain. π indicates lowest risk of weight gain. D indicates the greatest risk of diabetes and dyslipidemia (increase in triglycerides and a decrease in HDL).
From the data in this study the largest weight gain also poses the greatest risk for diabetes which makes sense. In fact, the two are associated, it’s called diabesity as I’ve mentioned in the chapter on obesity. Many other drugs in this list cause big gains in weight-ones that are not supposed to make you fat. If you happen to get really fat on another drug generally thought to be less risky, all of the other risk factors come with it such as increased chance of developing diabetes, hypertension, dyslipidemia and heart disease. With that comes heart attack and stroke the natural sequelae from inflammation which is what the metabolic syndrome is-an inflammatory disease. In other words AAP’s (and the SSRI’s) are very pro-inflammatory affecting your endothelium in a severe way.
Anywhere from 70 to over 90 patients die per year from AAP overdose and toxicity. They are not just bad for you they are bad to you. Let’s look at the Black Box warnings for Clozaril the first AAP to hit the market:
Clozapine also carries eleven black box warnings for agranulocytosis, CNS depression, leukopenia, neutropenia, seizure disorder, bone marrow suppression, dementia, hypotension, myocarditis, orthostatic hypotension (with or without syncope) and seizures.[3]
If you must take an atypical (a small percentage may need to only if exercise 7 days a week and/or therapy fails first) then at least ask your doctor if you can get on metformin as well. Metformin has been shown to help prevent metabolic complications in patients taking an atypical.[4]These data are provided because I want you to know the risks in taking an AAP. If you are taking one get to the bottom of why are you on it. Most indications are weak, written by primary care doctors not psychiatrists. You need to get off of it before it harms or even kills you. Below I outline the simple yet reliable technique I use to wean patients off of these dreadful drugs.
As you can see from the timeline the newer materials started becoming popular in the 90’s. They replaced the older tricyclic antidepressants (TCA’s) because they weren’t as sedating or drying. Anyone who takes Elavil (a TCA) knows how dry your mouth can get or worse. These are called the anticholinergic side effects which are generally dry mouth, blurry vision, difficulty urinating, and sexual dysfunction. The sedation is from theantihistamine side effect. Think of Benadryl as the quintessential antihistamine-very sedating but it also has a powerful anticholinergic profile so you see dry mouth and urinary retention. Taking high-dose Benadryl is not unlike a dose of Elavil.
In addition it was found that the SSRI’s could treat anxiety quite well and were able to be used instead of addicting drugs like Valium. Valium is fine for very short periods of time say 1-2 weeks. After that a tolerance quickly mounts and soon an addiction can develop. Furthermore, Valium has a very long half life leading to a pretty powerful hangover the next day and it can interfere with work. If you become addicted stopping Valium at this point produces the exact effects you were being treated for, only stronger. So you see enhanced insomnia, profound anxiety and so forth. Not a great deal for the one stuck taking Valium (or any other in the benzodiazepine class) chronically. When that’s all over you still have anxiety and insomnia because you never addressed the root cause(s).
That’s why the SSRI’s were so acceptable. You could now treat anxiety and depression with one pill and leave them on it basically forever. At the time, they felt it was completely safe and non-addicting. They also found that some-the ones that also blocked reuptake of norepinephrine-could treat pain. So you have a drug with fewer side effects, especially the ones that really bother people like dry mouth and sedation, “non-addicting”, with anxiolytic and anti-depressive effects, and it’s dosed once per day. While some types can replace Elavil for the treatment of chronic pain like peripheral neuropathy (from diabetes) or post-herpetic neuralgia without the patient being knocked out and given cotton mouth.
That was how it all got started. I read how meperidine got going as well. Meperidine or Demerol® was the first synthetic narcotic hailed as non habit forming at the time it was introduced back in the 30’s. Well it didn’t take long before half the surgeons in the country were addicted to it. That’s how well we know if a new drug is addicting. Likewise we now know that for about half the population taking an SSRI it is next to impossible to withdraw from acutely without as Ann Blake Tracy would say going postal-wanting to jump out of a car at 80 mph.
THE LOW SEROTONIN & CHEMICAL IMBALANCE THEORIES OF DEPRESSION
Because psychiatry deals with the mind and they wish to remain in the reductionist camp, they are constantly looking for a “physical” explanation for “mental” disease. After decades of research they are not much closer to providing a failsafe theory for depression or any other mental illness. Years ago the prevailing wisdom was that depressed patients had a chemical imbalance in their brain that led to depression. This was first thought to be a catecholamine imbalance, a decrease in the level of neurotransmitters in the brain like norepinephrine or dopamine. Neurotransmitters are chemicals that allow communication from brain cell to brain cell as part of an electrochemical signaling system. Later the theory was amended to single out low brain serotonin as the cause of depression. Serotonin is one of the neurotransmitters found in the brain. However, the vast majority of serotonin is located outside the brain in the gut and mesentery. The low serotonin idea was the prevailing theory when I was in medical school. It’s not surprising that the SSRI’s would be prescribed for this condition since they dovetail nicely with theory. SSRI’s increase the available serotonin within the depleted brain of the depressed patient. Once the serotonin level becomes normalized the patient no longer is depressed. Nice and neat.
Unfortunately both the chemical imbalance and the low serotonin theories are incorrect. As early as 1983 while I was being taught the low serotonin theory the National Institutes of Mental Health (NIMH) concluded that there is no evidence that anything is wrong with the serotonergic system in depressed patients.
Later in 2009 at the Neuroscience conference in Chicago Illinois, Dr Eva Redei, a long time researcher in depression, found strong indications that depression is the result of some sort of dysfunction of your neurons (brain cells), that stress does not cause depression and that decreased levels of neurotransmitters-a popular press belief-are not involved in depression. Moreover the medications are focusing on the effect, not the cause, of depression which is why more than half the patients prescribed antidepressants for depression never get relief.[5]
NOW YOU KNOW THAT THE THEORIES OF DEPRESSION ARE WRONG. DRUGS THAT INCREASE SEROTONIN TO TREAT DEPRESSION HAVE NO THEORY TO SUPPORT THEIR USE. WE ALSO SEE FROM ABOVE THAT THE NEWER AAP’S HAVE A PORTFOLIO OF COMPLICATIONS SUCH AS MASSIVE WEIGHT GAIN, DIABETES, HEART ATTACK AND STROKE. IN THE NEXT PUBLICATION WE’LL REVIEW DR IRVING KIRSCH’S  NEW BOOK THE EMPEROR’S NEW DRUG WHERE HE SHOCKED THE COUNTRY WHEN HE FOUND OUT THAT ALL OF THESE NEWER DRUGS-THE SSRI’S-WORK NO BETTER THAN PLACEBO-A SUGAR PILL. WE’LL ALSO GO OVER EVEN MORE SHOCKING NEWS THAT THESE DRUGS DO IN FACT INDUCE MURDER, MAYHEM, AND SUICIDES.


[1] Joseph A. Lieberman III, M.D., M.P.H. History of the Use of Antidepressants in Primary Care. (http://www.psychiatrist.com/pcc/pccpdf/v05s07/v05s0702.pdf)
[2] Nasrallah HA, Newcomer JW  Atypical antipsychotics and metabolic dysregulation: evaluating the risk/benefit equation and improving the standard of care. (J Clin Psychopharmacol. 2004 Oct;24(5 Suppl 1):S7-14) 04/26/2012
[4] Pramyothin PKhaodhiar L. Metabolic syndrome with the atypical antipsychotics.(Curr Opin Endocrinol Diabetes Obes. 2010 Oct;17(5):460-6) 04/26/2012
[5] The Dangers of Taking Antidepressants with Aspirin (http://articles.mercola.com/sites/articles/archive/2011/11/04/antidepressants)