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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 14 of 14. This is the beginning of the thread.
Posted by RedHeadRed on June 2, 2004, at 11:46:37
For any of you that are interested in the bio-psychiatry of SSRIs, and their effects on the human body.. I have found a great article, the information is well supported with creditable medical publications.
The author of the article explored the connection between SSRIs and the pineal gland, but also reviews some of the basics of the bio-psychiatry of SSRIs before proposing his hypotheses.
_________________________________________
The Serotonergic System, the Pineal Gland & Side-Effects of Serotonin Acting Anti-Depressantshttp://www.antidepressantsfacts.com/pinealstory.htm
_________________________________________This article is very thorough, and a bit of an intensive read.. but it is highly educational.
Highlights:
- Medication classified "Re-Uptake Inhibitors" act on these transporter proteins and thereby inhibit the re-uptake of neurotransmitters back into the synapse of the firing neuron. SSRI-AntiDepressants or Selective Serotonin Re-uptake Inhibitors, belong to this class of medication. Each group of neurons fire specific neurotransmitter-molecules. The neurotransmitter Serotonin, also known as 5-Hydroxy-Tryptamine (5-HT) is such a molecule.
- Next to be a muscle- and vasoconstrictor, serotonin plays an important role in sleep, appetite, memory, sexual behaviour, respiratory activity, aggression, motor output, sensory and neuroendocrine function, but most important, perception!
- What actually happens when you increase serotonergic neuronal activity or elevate your serotonin levels is this: the stress hormones "Cortisol" & "Adrenaline" (Epinephrine) in the brain and body are triggered by increased serotonergic activity or elevated serotonin levels. It is a natural reaction from the body to combat the excessive serotonin levels. These released hormones, cortisol and adrenaline, are secreted from the "Adrenal Glands."
- If a patient continues to ingest a particular SSRI-antidepressant over a prolonged period of time, eventually the bodies Adrenal Glands may lose their efficiency and "Adrenal Exhaustion Syndrome" will be the end result. Adrenal Exhaustion causes levels of adrenaline initially to fall and levels of cortisol to rise. Many (former) SSRI-AntiDepressant users reported fatigue as a long term side-effect or were diagnosed with "Chronigue Fatigue Syndrome."
- Nicholas Giarmin, a professor of pharmacology and Daniel Freedman, a professor of psychiatry, confirmed that the human brain manufactures serotonin at various sites in the brain. For example, in the Thalamus, they discovered 61 nanograms of serotonin per gram of tissue; in the Hippocampus, 56 ng.; in the Central Gray Section of the Midbrain, they found 482 ng. But in the Pineal Gland, they found 3140 ng. of serotonin per gram of tissue. The Pineal Gland was unmistakably the richest site of serotonin in the brain! This discovery implicates the Pineal Gland as an important site of serotonergic activity.
- A malfunctioning Pineal Gland and disturbances in serotonin and melatonin secretion could also lead to excessively secreted hormones of the Endocrine System.
- An under-active serotonergic system will be a result of (1)the damaged axon terminals at the firing part of the serotonergic neuron and/or (2)the eliminated receptors at the dendrites of the receiving part of the serotonergic neuron. When discontinuing an SSRI-AntiDepressant, serotonergic activity dramatically decreases because the neurons aren't able to communicate properly with each other anymore. As a result of this decreased serotonergic activity, side-effects occur, which are falsely defined as "withdrawal side-effects."
- Whether or not the function of the Pineal Gland gets affected by SSRI-AntiDepressants, either owing to a metabolic deficiency, or damaged serotonergic nerve terminals and receptors, or as a result of a hyperactive serotonergic system, needs to be established. A malfunctioning Pineal Gland could lead to disturbances in the natural circadian rhythm of melatonin secretion, as well as disturbances in glucose metabolism in the brain and an overall decrease of brain and blood levels of glucose. Hence, the natural defence to epileptic activity in the brain will fall off, as well as the natural defence to a hyperactive Endocrine System.
___________________________
Sometimes, it just amazes me how complex the human body is...
Posted by linkadge on June 2, 2004, at 13:13:10
In reply to Bio-psychiatry of SSRIs - Article, posted by RedHeadRed on June 2, 2004, at 11:46:37
I've heard the SSRI adrenal exhaustion theory before. I've also heard the counter to the argument that notes that the antidepressant effect often begins when HPA axis activity is normalized.
Linkadge
Posted by Sad Panda on June 2, 2004, at 14:13:26
In reply to Re: Bio-psychiatry of SSRIs - Article, posted by linkadge on June 2, 2004, at 13:13:10
> I've heard the SSRI adrenal exhaustion theory before. I've also heard the counter to the argument that notes that the antidepressant effect often begins when HPA axis activity is normalized.
>
> Linkadge
>
>I think it all has to do with how well you tolerate a particular drug not that it is or isn't a SSRI. I went haywire on Prozac, it pushed my TSH levels up while trying to make me psychotic, by contrast, Effexor has been like sipping milk & yet people say it is poison. :)
Cheers,
Panda.
Posted by Questionmark on June 3, 2004, at 1:20:55
In reply to Re: Bio-psychiatry of SSRIs - Article » linkadge, posted by Sad Panda on June 2, 2004, at 14:13:26
This article scares the heck out of me. The specific reasons for SSRI withdrawal, and the gradual elevation of cortisol along with the gradual decrease in epinephrine secretion-- this would all make perfect sense. And yes, maybe SSRIs still increase neuronal regeneration and/or synaptic plasticity in the hippocampus-- due to the increase in intrasynaptic serotonin levels-- but they could still damage serotonergic neurons/axons and postsynaptic dendrites as well. And the whole thing about cortisol and epinephrine-- why cOUldn't that be true? What if it is? Maybe it's another partial explanation for SSRI-induced anhedonia (in addition to the decrease in dopamine transmission). Ah man.
What if we are just naive about our reliance on psychoactive medications? If we are then i am one of the most naive. Yes some people would need them anyway-- i probably even would still-- but are the long-term neurobiological effects usually negative??
i'm not on an SSRI (though i was on Paxil for two years and experienced months of inexplicable despair after stopping it) but i am on Nardil and that is extremely serotonergic as well. But who knows if unnaturally elevated and sustained increases in other neurotransmitter levels could have negative consequences, too?
i'm so sorry to be so negative and discouraging. i'm just so worried about this. i want someone to logically tell me that i'm wrong, and that this isn't true. Someone please convince me.
Crap.
Posted by Sad Panda on June 3, 2004, at 2:46:25
In reply to Re: Bio-psychiatry of SSRIs - Article (!!!), posted by Questionmark on June 3, 2004, at 1:20:55
> This article scares the heck out of me.
>
>It's supposed to scare you, that's what the website is all about. It call's itself "AntidepressantsFacts" but the only actual fact is in the 7th paragraph: "scientists are still not sure why serotonin boosters seem to alleviate depression"
Cheers,
Panda.
Posted by linkadge on June 3, 2004, at 9:09:01
In reply to Re: Bio-psychiatry of SSRIs - Article (!!!) » Questionmark, posted by Sad Panda on June 3, 2004, at 2:46:25
Quite a few people have genes that code for very low MAO-A to begin with. Does this mean that they are born with a brain that poisons itself with serotonin ??? Of course not.
As well, there is a coding for a short allele and long allele (about 40 percent of the population has it) which codes for a 2 fold change in the reputake of serotonin. Do these changes imply natural neurotoxicity.
It is well known that SSRI's *prevent* the axonal dammage due to ecstacy use.
As well paxil prevents the HD neurodenegeration process. Check out www.hdlighthouse.org
The *only* studies I have seen linking SSRI's to neuonal dammage were the ones that use 50, and 100 times the maximum human dose of prozac.
And this could have easily been caused by the harsh dirtyness of prozac to begin with.My rule of thum is this. Take enough that you feel normal, no more. When this happens it is very likely that your brain is much heathier than with no meds at all.
Also note that the *majority* of studies on SSRI's show a HPA axis normalization after continued use.
Linkadge
Posted by linkadge on June 3, 2004, at 9:10:02
In reply to Think of it this way Questionmark, posted by linkadge on June 3, 2004, at 9:09:01
Oh and many chinees herbs are potent 5-ht receptor agonists.
Linkadge
Posted by Questionmark on June 3, 2004, at 11:25:10
In reply to Think of it this way Questionmark, posted by linkadge on June 3, 2004, at 9:09:01
Posted by Marilyn on June 4, 2004, at 5:05:42
In reply to Think of it this way Questionmark, posted by linkadge on June 3, 2004, at 9:09:01
>Quite a few people have genes that code for very low MAO-A to begin with. Does this mean that they are born with a
>brain that poisons itself with serotonin ??? Of course not.
>As well, there is a coding for a short allele and long allele (about 40 percent of the population has it) which
>codes for a 2 fold change in the reputake of serotonin. Do these changes imply natural neurotoxicity.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14982105
J Psychosoc Nurs Ment Health Serv. 2004 Feb;42(2):16-20.Serotonin syndrome and the use of SSRIs.
Finfgeld DL.
Sinclair School of Nursing, University of Missouri, Columbia, Missouri 65211, USA. finfgeldD@health.missouri.edu
Nurses need to become more aware of serotonin
syndrome to avoid its development and to ensure a therapeutic response when early symptoms emerge. While polypharmacy tends to put individuals at greatest risk for the syndrome, use of a single serotonergic agent may also provoke an adverse response. Because the onset and progression of serotonin syndrome are rapid, prompt action may be needed to avoid potentially life-threatening consequences.Pain Med. 2003 Mar;4(1):63-74.
Serotonin syndrome and other serotonergic disorders.
Ener RA, Meglathery SB, Van Decker WA, Gallagher RM.
MCP Hahnemann University Hospitals, Philadelphia, Pennsylvania 19102, USA. rae22@drexel.edu
Serotonin syndrome is an iatrogenic disorder induced by pharmacologic treatment with serotonergic agents that increases serotonin activity. In addition, there is a wide variety of clinical disorders associated with serotonin
excess. The frequent concurrent use of serotonergic and neuroleptic drugs and similarities between serotonin
syndrome and neuroleptic malignant syndrome can present the clinician with a diagnostic challenge. In this article, we review the pathophysiology, diagnosis, and treatment of serotonin syndrome as well as other serotonergic
disorders.
>It is well known that SSRI's *prevent* the axonal dammage due to ecstacy use.
>As well paxil prevents the HD neurodenegeration process. Check out www.hdlighthouse.org
>The *only* studies I have seen linking SSRI's to neuonal dammage were the ones that use 50, and 100 times the
>maximum human dose of prozac. And this could have easily been caused by the harsh dirtyness of prozac to begin with.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12717649
Rev Neurol. 2003 Apr 16-30;36(8):724-6. Related Articles, LinksNeonatal convulsions and subarachnoid hemorrhage after in utero exposure to paroxetine
[Article in Spanish]
Salvia-Roiges MD, Garcia L, Gonce-Mellgren A, Esque-Ruiz MT, Figueras-Aloy J, Carbonell-Estrany X.
Servei de Neonatologia, Institut Clinic de Ginecologia, Obstetricia, i Neonatologia, Unitat Integrada de Pediatria,
(ICGON), Barcelona, Espana. dsalvia@clinic.ub.esINTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) are often used as antidepressants in pregnant women. SSRIs do not appear to increase the teratogenic risk when used in their recommended doses. However, not enough
information is available at this time about the risk of toxicity and complications in newborns, after mother treatment with SSRI during the third trimester of pregnancy. We are limited to the existing reports that describe newborns with symptoms due to hyperserotoninemia or withdrawal. CASE REPORT: One newborn whose mother had been
treated with paroxetine 20 mg/day during pregnancy, presented convulsions and subarachnoid haemorrhage in the first six hours of life. The newborn did not present symptoms of hypoxic ischaemic encephalopathy, withdrawal syndrome,
infection, metabolic alterations, cerebral malformations or coagulopaties. DISCUSSION: The most probable etiology is that the paroxetine could decrease the seizure threshold, taking place the first seizure during delivery.
The difficult fetal extraction would have provoked the subarachnoid haemorrhage in a patient with an impaired haemostatic function due to a depletion of platelet serotonin and may also contribute the increased vascular fragility due to paroxetine and reported in adults or in animals. CONCLUSION: Neonatal convulsions and subarachnoid haemorrhage may occur after paroxetine treatment in the third trimester of pregnancy. An accurate follow up of
these newborns in the firsts days of life is strongly recommended.http://www.neurology.org/cgi/content/abstract/58/1/130
Neurology 2002;58:130-133
© 2002 American Academy of NeurologyCerebral vasoconstriction and stroke after use of serotonergic drugs
A. B. Singhal, MD, V. S. Caviness, MD, A. F. Begleiter, MD, E. J. Mark, MD, G. Rordorf, MD and W. J. Koroshetz, MD
Serotonin (5-hydroxytryptamine) is a potent vasoconstrictor amine. The authors report three patients who developed thunderclap headache, reversible cerebral arterial vasoconstriction, and ischemic strokes (i.e., the Call-Fleming
syndrome). The only cause for vasoconstriction was recent exposure to serotonergic drugs in all patients, and to pseudoephedrine in one patient. These cases, and the literature, suggest that the use of serotonin-enhancing drugs can precipitate a cerebrovascular syndrome due to reversible, multifocal arterial narrowing.>My rule of thum is this. Take enough that you feel normal, no more. When this happens it is very likely that your
>brain is much heathier than with no meds at all.Ann Pharmacother. 2003 Feb;37(2):209-11. Related Articles, Links
Serotonin syndrome induced by low-dose venlafaxine.
Pan JJ, Shen WW.
Department of Psychiatry, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan.
OBJECTIVE: To report the case of a patient with serotonin syndrome induced by low-dose venlafaxine. CASE SUMMARY:
A 29-year-old Taiwanese woman with major depressive disorder abruptly developed serotonin syndrome during low-dose (37.5 mg/d) venlafaxine monotherapy, with symptoms of restlessness, tremor, shivering, diarrhea, vomiting, ataxia,
tachycardia, and myoclonus. The patient recovered in 2 hours after receiving prochlorperazine and lorazepam in the emergency department. Venlafaxine was discontinued, and she was discharged home. Two weeks later, the patient
started to receive fluoxetine 20 mg/d and reported no adverse adverse effects during follow-up clinic visits. DISCUSSION: The clinical manifestations of this case meet Sternbach's criteria of serotonin syndrome. Its possible
etiologic factors include panic attack, adverse drug reaction, pharmacodynamic interaction, and congenital absence of CYP2D6 enzyme activity. The Naranjo probability scale suggested a probable causality of venlafaxine treatment and serotonin syndrome. CONCLUSIONS: Clinicians should be aware of the risk of serotonin syndrome when the patient receives not only a combination of 2 antidepressants, but also the single potent serotonergic agent venlafaxine.
>Also note that the *majority* of studies on SSRI's show a HPA axis normalization after continued use.HPA axis "normalization" is not necessarily accompanied by clinical improvement of depression:
Psychiatry Research
Volume 120, Issue 3 , 15 October 2003, Pages 257-264
Influence of mirtazapine on urinary free cortisol excretion in depressed patientsCornelius Schule, Thomas Baghai, Constanze Rackwitz and Gregor Laakmann,
Department of Psychiatry, University of Munich, Nüssbaumstr. 7, Munich 80336, GermanyMirtazapine has been shown to acutely inhibit cortisol secretion in healthy subjects. In the present study, the impact of mirtazapine treatment on urinary free cortisol (UFC) excretion was investigated in depression. Twenty
patients (six men, 14 women) suffering from major depression according to DSM-IV criteria were treated with mirtazapine for 3 weeks. The patients received 15 mg mirtazapine on day 0; 30 mg mirtazapine on day 1; and 45 mg mirtazapine per day from day 2 to the end of the study (day 21). UFC excretion was measured before treatment (day 1), at the beginning (day 0), after 1 week (day 7) and after 3 weeks (day 21) of treatment with mirtazapine. Urine samples were collected from 08:00 to 08:00 h the following day. On the days of urine sampling, the severity of
depressive symptoms was assessed using the 21-item version of the Hamilton Rating Scale for Depression (21-HAMD). There was a significant reduction of UFC excretion during 3-week mirtazapine therapy, which was already obvious
after the first day of treatment (day 0). However, there were no significant across-subjects correlations between UFC reduction and decrease in 21-HAMD sum scores. Apparently, the mirtazapine-induced rapid reduction of cortisol
secretion in depressed patients is not necessarily correlated with a favorable therapeutic response.World J Biol Psychiatry. 2001 Apr;2(2):103-5. Related Articles, Links
Attenuation of HPA axis hyperactivity and simultaneous clinical deterioration in a depressed patient treated with mirtazapine.
Schule C, Baghai T, Zwanzger P, Rupprecht R.
It has been suggested that hypothalamic-pituitary-adrenal (HPA) system dysregulation plays an important role in the pathophysiology of depression and that normalization of HPA axis hyperactivity precedes successful treatment with
antidepressants. We report the case of a 61-year-old patient suffering from a major depressive episode who underwent the combined dexamethasone suppression/CRH stimulation test (DEX/CRH test) before and again after one week of mirtazapine treatment. While the patient showed a marked decrease of cortisol and ACTH secretion during the DEX/CRH test within one week, a pronounced and ongoing deterioration of depressive symptoms with suicidal thoughts occurred that was resistant to antidepressant medication and had to be treated with electroconvulsive therapy. Apparently, mirtazapine rapidly attenuates HPA axis hyperactivity in depressed patients via direct pharmacoendocrinological effects. However, this amelioration of HPA system dysregulation is not necessarily accompanied by clinical
improvement.> Quite a few people have genes that code for very low MAO-A to begin with. Does this mean that they are born with a brain that poisons itself with serotonin ??? Of course not.
>
> As well, there is a coding for a short allele and long allele (about 40 percent of the population has it) which codes for a 2 fold change in the reputake of serotonin. Do these changes imply natural neurotoxicity.
>
> It is well known that SSRI's *prevent* the axonal dammage due to ecstacy use.
>
> As well paxil prevents the HD neurodenegeration process. Check out www.hdlighthouse.org
>
>
> The *only* studies I have seen linking SSRI's to neuonal dammage were the ones that use 50, and 100 times the maximum human dose of prozac.
> And this could have easily been caused by the harsh dirtyness of prozac to begin with.
>
> My rule of thum is this. Take enough that you feel normal, no more. When this happens it is very likely that your brain is much heathier than with no meds at all.
>
> Also note that the *majority* of studies on SSRI's show a HPA axis normalization after continued use.
>
>
> Linkadge
>
>
>
>
Posted by linkadge on June 4, 2004, at 8:53:31
In reply to Re: Think of it this way Questionmark, posted by Marilyn on June 4, 2004, at 5:05:42
You gave a bunch of reports saying the dangers of "serotonin syndrome". We all know serotonin syndrome is bad. Plus, a drug that does not cause SS initially, has virtually no risk of causing it down the road, so long as the dose is maintained.
I think the posiives far outweigh the negatives
which are relatively unlikely to occur.
http://www.eurekalert.org/pub_releases/2003-08/wuso-adm072803.phphttp://www.globaltechnoscan.com/24thOct-30thOct01/antidepressants.htm
http://www.nature.com/nsu/030804/030804-11.html
http://mdma.net/protect/prozac.html
Linkadge
Posted by Marilyn on June 8, 2004, at 8:11:11
In reply to I'm sorry I don't understand ???, posted by linkadge on June 4, 2004, at 8:53:31
>> I think the posiives far outweigh the negatives which are relatively unlikely to occur.
I am sorry to disappoint you, but I don't think so:
"Published results from one trial of paroxetine and two trials of sertraline suggest equivocal or weak positive risk-benefit profiles. However, in both cases, addition of unpublished data indicates that risks outweigh benefits. Data from unpublished trials of citalopram and venlafaxine show unfavourable risk-benefit profiles."
http://www.antidepressantsfacts.com/Lancet-SSRIs-childhood-depression.htmHealth Canada advises Canadians of stronger warnings for SSRIs and other newer anti-depressants
http://www.hc-sc.gc.ca/english/protection/warnings/2004/2004_31.htmMarilyn
Posted by Sad Panda on June 8, 2004, at 9:40:56
In reply to Re: I'm sorry I don't understand ???, posted by Marilyn on June 8, 2004, at 8:11:11
> I am sorry to disappoint you, but I don't think so:
> "Published results from one trial of paroxetine and two trials of sertraline suggest equivocal or weak positive risk-benefit profiles. However, in both cases, addition of unpublished data indicates that risks outweigh benefits. Data from unpublished trials of citalopram and venlafaxine show unfavourable risk-benefit profiles."
> http://www.antidepressantsfacts.com/Lancet-SSRIs-childhood-depression.htm
>
> Marilyn
>
Hi Marilyn,I think that particular website might have a very blinkered view of antidepressants & is not a reliable source for data.
Cheers,
Panda.
Posted by Marilyn on June 8, 2004, at 21:40:19
In reply to Re: I'm sorry I don't understand ??? » Marilyn, posted by Sad Panda on June 8, 2004, at 9:40:56
>> "Published results from one trial of paroxetine and two trials of sertraline suggest equivocal or weak positive risk-benefit profiles. However, in both cases, addition of unpublished data indicates that risks outweigh benefits. Data from unpublished trials of citalopram and venlafaxine show unfavourable risk-benefit profiles."
>> http://www.antidepressantsfacts.com/Lancet-SSRIs-childhood-depression.htm
>> Marilyn>Hi Marilyn,
>
> I think that particular website might have a very blinkered view of antidepressants & is not a reliable source for data.
>
> Cheers,
> Panda.Hi Panda,
Well it might be, but does that make the abovementioned study which is recently published in the Lancet Journal suddenly less true?
You can access this article on the own website of the Lancet at the following URL: http://www.thelancet.com/journal/vol363/iss9418/full/llan.363.9418.original_research.29377.1You need to register before you can access it.
Marilyn
Posted by Sad Panda on June 9, 2004, at 1:20:54
In reply to Re: I'm sorry I don't understand ???, posted by Marilyn on June 8, 2004, at 21:40:19
> >> "Published results from one trial of paroxetine and two trials of sertraline suggest equivocal or weak positive risk-benefit profiles. However, in both cases, addition of unpublished data indicates that risks outweigh benefits. Data from unpublished trials of citalopram and venlafaxine show unfavourable risk-benefit profiles."
> >> http://www.antidepressantsfacts.com/Lancet-SSRIs-childhood-depression.htm
>
> >> Marilyn
>
> >Hi Marilyn,
> >
> > I think that particular website might have a very blinkered view of antidepressants & is not a reliable source for data.
> >
> > Cheers,
> > Panda.
>
> Hi Panda,
>
> Well it might be, but does that make the abovementioned study which is recently published in the Lancet Journal suddenly less true?
> You can access this article on the own website of the Lancet at the following URL: http://www.thelancet.com/journal/vol363/iss9418/full/llan.363.9418.original_research.29377.1
>
> You need to register before you can access it.
>
> Marilyn
>
>Ahh, I'm with you now, it about giving SSRI's to CHILDREN due increased risk of a paradoxial reaction, ie, SSRI's may increase suicidal & violent behaviour. My personal view is that children should be given TCA's rather than SSRI's & only when absolutely neccessary.
Cheers,
Panda.
This is the end of the thread.
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