![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 19 of 19. This is the beginning of the thread.
Posted by Maoiman on June 16, 2009, at 15:59:39
Hi there everyone,
Perhaps somebody has a suggestion on how to handle this:
Sense of mounting desperation and impending doom.
Suicidal thoughts, (even planning the method, location.) I've had 3 major depressive episodes, all were preceeded by a couple of weeks of euphoria, then crash, (for many months). No substance abuse, just boughts of various meds, all pooped out after 3-8 months. these were,
Venlafaxine, Amisulpride, Sulpride, Tianeptine,
Moclobemide, Bupropion, Reboxetine, Fluoxetine various benzos and sleep meds. Some like the SSRI's caused uncharacterist behaviors . Could this be bipolar? if yes is there any solutions other than heavy duty meds like Lithium, Valproate
( which I've never tried, too scared)Any suggestions most welcome.
Thanks.
MM.
Posted by Amelia_in_StPaul on June 16, 2009, at 18:33:35
In reply to How would you medicate this?, posted by Maoiman on June 16, 2009, at 15:59:39
The euphoria followed by a crash leads me to immediately think bipolar II. Esp. since med trials have failed. I understand your fear of mood stabilizers, I really really do, it's always scary to jump from one class of drugs to another, esp. if the first class was hard to deal with, but if ADs aren't working, you really need to try something else...alternately, you could try ECT or see if you would be a candidate for TMS.
Woah--just reread. Are you still planning suicide? Get thee to ER right away if so...
Best of luck to you. Meds are a b&tch, I know...
> Hi there everyone,
> Perhaps somebody has a suggestion on how to handle this:
> Sense of mounting desperation and impending doom.
> Suicidal thoughts, (even planning the method, location.) I've had 3 major depressive episodes, all were preceeded by a couple of weeks of euphoria, then crash, (for many months). No substance abuse, just boughts of various meds, all pooped out after 3-8 months. these were,
> Venlafaxine, Amisulpride, Sulpride, Tianeptine,
> Moclobemide, Bupropion, Reboxetine, Fluoxetine various benzos and sleep meds. Some like the SSRI's caused uncharacterist behaviors . Could this be bipolar? if yes is there any solutions other than heavy duty meds like Lithium, Valproate
> ( which I've never tried, too scared)
>
> Any suggestions most welcome.
>
> Thanks.
> MM.
>
Posted by Phillipa on June 16, 2009, at 21:47:36
In reply to Re: How would you medicate this? » Maoiman, posted by Amelia_in_StPaul on June 16, 2009, at 18:33:35
First you're new welcome to babble. Amelia is right contact your doc or a hotline and get into the hospital ASAP as you have a plan that is serious. What's the plan sometimes talking helps to put things in perspective? Love Phillipa
Posted by rjlockhart04-08 on June 16, 2009, at 22:16:18
In reply to How would you medicate this?, posted by Maoiman on June 16, 2009, at 15:59:39
Depending on what situation, in sub-counsious level, and counsious levels of alertness/awareness of what currently happening, what could happen, past memories (sub counsious).
Lithium, and Topamax do level mood swings. Lithium is more effective, yet it's very old.
Only issue it keeps you "in one" state, so you don't get euphoric, or happy when you go to a party, your just "stable". Cut's some Charasmatic skills off, because your not in mood, or not "in the moment". Lithium all i know, stablizes, nuerons and protons, back to normal.
Yet, with lithium you have to have blood checks, because of levels, just for safety.Prozac has been, out of all, the generic 40mg has work'd, better than any other. Depends on a person's personality, and diffrent charasteric's in DNA.
Impending Doom....oh yes, i've had the feeling, and then experienced it! yes! profacy! thank you god!
It's the faith, or the belief that you know that it's going to get work'd out no matter what happens, (anything). Just keep believing, tommorow will bring something.My doctor, Lamictal (anticonvultant/moodstablizer) at 100mg, but at 75mg now. It's good, only major concern is the "rash". Which, is, can't say the chances. 150mg i was going to move up, yet someone manipulated my own doctor, so have to go with the flow.
Haloperidol is the "med" you would scream at....
that is the "scary, get that away from me!"
Some evil nurse forcing it down your throught....(nightmare!)That's all i can give/ right now. Research for ya, yet, there is only limited time, because i'm trying to help, yet there is a "beast" that lives here. Snatch's the computer! mean...
takecare
rj
Posted by morganpmiller on June 17, 2009, at 5:01:22
In reply to Re: How would you medicate this?, posted by rjlockhart04-08 on June 16, 2009, at 22:16:18
I personally think Lamictal is a dirtier drug than what many believe it to be. It depletes your body of folic acid and other essential vitamins/minerals. It also binds to your melanin in the skin and eyes and they admit to having no idea whether that will have any long term implications.
Lithium and Valproate(Depakote) are not as heavy duty or as harsh as you think. It is the high toxic doses of these medications used by so many that give these meds their bad names. Some may just benefit from lower doses, especially if they are somewhat stabilized on an antidepressant.
ECT is an option. I would try to find the right medication/therapy before I did ECT. You really should consider finding some good old therapy if you can. I would especially recommend group therapy conducted by 2 good psychotherapist. This is the best type of therapy I have experienced.
Posted by rjlockhart04-08 on June 17, 2009, at 6:29:44
In reply to Re: How would you medicate this?, posted by morganpmiller on June 17, 2009, at 5:01:22
then why did they patent Lamicatal?
to improve old method's. Depends on anyone.
Posted by rjlockhart04-08 on June 17, 2009, at 7:45:29
In reply to Re: How would you medicate this?, posted by rjlockhart04-08 on June 17, 2009, at 6:29:44
not...as a provocation to your post. There constantly new new new! Stay basic..eventually it will get so advanced ,New generation medications, have more "inner side effects"
sometimes just i think keep it basic. Like the old day's, yet, they had their bad times. Barbiturates, yet you knew exactly the side effect of it.
serious...
Posted by Maoiman on June 17, 2009, at 12:17:11
In reply to Re: How would you medicate this? » Maoiman, posted by Amelia_in_StPaul on June 16, 2009, at 18:33:35
Thank you all for the advice, don't worry the suicide is the final option and it's not yet there. For the moment I still have fight in me. Maybe give Neurontin a try first. Lamictal sounds ok, but I'll wait with that.Thanks again
MM.
Posted by Zana on June 17, 2009, at 14:48:20
In reply to Re: How would you medicate this? thanks to all for, posted by Maoiman on June 17, 2009, at 12:17:11
Do you have a good pdoc? I ask because it sounds very clearly like you are describing mood swings- something on the bipolar spectrum, but I don't see anything in you med history that addresses this. There are many different mood stabilizers. Pdocs now divide them into top down or bottom up meaning some are more likely to bring your mood down, some are more likely to elevate it. I think you sound like a good candidate for a trial on something that will level you out without blunting you. I sounds like you need to work with someone skillful and sxperienced in treating bipolar since you are experiencing both the tops- euphoria- and the pits- the depression. And don't despair. For better or for worse, you have just scratched the tip of the medication iceberg.
Zana
Posted by Maoiman on June 17, 2009, at 15:16:18
In reply to Re: How would you medicate this? thanks to all for, posted by Zana on June 17, 2009, at 14:48:20
Thanks for your post Zana,
I've just started with a new Pysch.Dr. it remains to be seen if she is any good. The previous ones going back some years only saw me in a depressive ( severely) state, I only wanted them to provide the means to get me back to that energetic, creative "high" that I functioned best in.
Lately though I feel that the options are narrowing, and that my own brain is finding ever faster and sneaky little ways to close off the escape routes. I guess you and most on this board know exactly what I'm talking about.
Nevertheless the battle will go on! and sooner or later I'll have pluck up the courage and try those "Mood stabilizers".
Thanks,
MM
Posted by morganpmiller on June 18, 2009, at 3:00:02
In reply to Re: How would you medicate this? thanks to all for » Zana, posted by Maoiman on June 17, 2009, at 15:16:18
Why not try a low dose of lithium? 200 to 300 mgs of the extended release form, lithobid. You should not have any issues with this dosage. And, you can take it with many other medications. I posted a bunch of information about lithium here:
# Re: Anyone's experience taking lithium morganpmiller 6/17/09
Posted by morganpmiller on June 18, 2009, at 3:05:16
In reply to Re: How would you medicate this? thanks to all for » Zana, posted by Maoiman on June 17, 2009, at 15:16:18
The immunostimulating and antimicrobial properties of lithium and antidepressants
Purchase the full-text articleReferences and further reading may be available for this article. To view references and further reading you must purchase this article.
Julian LiebCorresponding Author Contact Information, a, E-mail The Corresponding Author
a22 Rimmon Road, Woodbridge, CT 06525, USA
Accepted 1 March 2004.
Available online 17 April 2004.Abstract
Eicosanoids are products of arachidonic acid (AA), an essential fatty acid. They include prostaglandins (PGs), prostacyclin (PGI2), thromboxanes (TXs), leukotrienes (LTs) and hydroxy fatty acids. AA is derived enzymatically from membrane phospholipids and to a lesser extent the diet. Eicosanoids self-regulate every cell, including those synthesizing serotonin, norepinephrine and dopamine and those subserving immune function, such as T-cells, B-cells, natural killer cells, macrophages, monocytes and dendritic cells. There is objective evidence that prostaglandins regulate the physiology of the hypothalamicpituitaryadrenal axis (HPA).
Elucidation of the structure and metabolic pathways of eicosanoids galvanized researchers into illuminating their role in physiology, pathology and pharmacology. Striking contradictions arose: eicosanoids were shown to activate and suppress microorganisms, potentiate and suppress immunity and possess pro- and anticancer properties. As prostaglandins are the most heavily studied eicosanoids in the context of mood and immunity I will focus on them in this article. I will present evidence of the immunostimulating and antimicrobial properties of lithium and antidepressants and propose that these properties are linked to the antiprostaglandin actions of these compounds.
Stimulating Immune Function With Lithium and Antidepressants
Submitted by MedHeadlines on 25 April, 2008 22:31No Comment
Email This Article Email This Article Print PrintBy Julian Lieb, M.D.
Stimulating immune function would transform the prevention, treatment, research and economics of infectious disorders, among them the acquired immunodeficiency syndrome (AIDS), hospital-acquired infections, antibiotic-resistant bacterial infections, resistant tuberculosis, a possible avian influenza pandemic and acts of bioterrorism. Immune stimulation is widely held to be beyond our reach, an unfortunate misconception, for as early as nineteen eighty-one published evidence showed that lithium (1) and antidepressants (2) have immune stimulating and antimicrobial properties (3).
Stimulating the immune function with lithium and antidepressantsIn the early 1950s physicians observed that patients treated for tuberculosis with the monoamine oxidase inhibitors isoniazid and iproniazid became animated and energized, the observation the first that drugs are capable of acting as antidepressants. That monoamine oxidase inhibitors have dual antimicrobial and antidepressant properties curiously failed to impact the pharmacology of infectious disorders. Remission of such manifestations of viral infections as sinusitis, bronchitis, frequent colds, sore throats, cold sores and genital herpes in patients taking lithium carbonate has been reported. In various studies chronic lithium therapy reduced the rate of recurrent labial herpes infections, while lithium and antidepressants reduced the rates of common, flu-like colds, and lithium reduced the frequency and duration of recurrences of genital herpes.
The white blood cells of a woman with recurrent staphylococcal and streptococcal skin infections were unresponsive to stimulation. Addition of lithium to her cells restored their response. After receiving lithium for five weeks she became free of infection, and relapsed when lithium was withdrawn. Lithium chloride prevents replication of type 1&2 herpes virus in baby hamster kidney cells, augments several immune reactions in laboratory settings, and enhances antibody synthesis in humans.
Antidepressants can remit tuberculosis, canker sores, cold sores, genital herpes, upper respiratory tract infections, plantar warts and reduce the frequency of recurrences of shingles, remit the pain of this disorder and prevent post-shingles pain. Antidepressants can destroy the organisms of various parasitic diseases, inhibit the growth of the intestinal parasite giardia lamblia, and have antimalarial properties. Antidepressants enhance susceptibility to chloroquine in resistant malaria, and can destroy such parasites as those of sleeping sickness. Antidepressants are lethal to disease causing fungi, remit recurrent vaginal candida, have antibacterial activity, and synergize antibiotics against several bacteria. Evidence to date shows that lithium has antiviral and antibacterial properties, while antidepressants have antiviral, antibacterial, antiparasitic, and fungicidal properties. While laboratory studies show that lithium and antidepressants have direct antimicrobial properties, their actions on the brain would seem to be responsible for their immune stimulating properties.
A therapeutic claim is reinforced when the mechanisms are known. Prostaglandins are ephemeral, infinitesimal and powerful lipid signalers that self-regulate every cell in the body, including those subserving mood and those subserving immune function, and differentiating between the function and dysfunction of every cell. Prostaglandins regulate the physiology, immunity, replication and toxicity of microbes, and the resistance of their hosts. When synthesized excessively prostaglandins depress immune function, allowing microbes to replicate. The failure of such anti-prostaglandin drugs as aspirin and ibuprofen drugs in infection led to the conclusion that prostaglandin inhibition has limited value in this context. The prostaglandin- inhibiting properties of lithium and antidepressants have been neglected, along with their unique immunopotentiating and antimicrobial actions. Lithium and every antidepressant tested inhibit prostaglandins in a more complex fashion than aspirin and ibuprofen, and act on a wider variety of enzymes. This probably accounts for lithium and antidepressants having powerful immune stimulating and antimicrobial properties, which aspirin and ibuprofen do not.
The relationship between prostaglandins and viruses has been studied intensively, especially the human immunodeficiency virus (HIV). Where HIV comes into contact with arachidonic acid, the precursor of prostaglandins, it converts it into prostaglandin E2, the most powerful, ubiquitous and immune suppressive of all prostaglandins, and possibly responsible for the immune suppression that is the hallmark of AIDS. An HIV protein powerfully induces prostaglandin E2 production, and humans with AIDS dementia have a marked increase in prostaglandin E2 in their spinal fluid.
Prostaglandins are present in high concentrations in the saliva of such blood-sucking insects as ticks. They are involved in parasite metabolism and physiology, facilitate feeding by increasing local blood flow, and prolong attachments of ticks by suppressing immune mechanisms. Release of prostaglandins by parasites plays a role in penetration, immune suppression, inflammation and modulation of blood clotting. Induction of prostaglandins is responsible for many of the symptoms of bacterial infection including the Immune suppression. Disease causing fungi produce and respond to prostaglandins. Prostaglandins regulate the physiology, immunity, reproduction and toxicity of microbes and the resistance of their hosts.
The depressive effect of bereavement and other stresses on immune function is well documented. Impaired immune function has been demonstrated in depressives, and antidepressants are known to stimulate immune function. While lithium is effective against some bacteria and viruses, evidence for its effectiveness against parasites and fungi is lacking. Antidepressants, on the other hand, are effective against various bacteria, viruses, parasites and fungi. As lithium and antidepressants have immunopotentiating as well as antimicrobial properties, they stand to be effective against a gamut of microbes. The response of infection to lithium and antidepressants mirrors the treatment of depression in which subjects respond to tricyclic antidepressants, specific serotonin reuptake inhibitors, monoamine oxidase inhibitors or lithium. An infection should not be labeled refractory to antidepressants until many, if not all have been tried. Many studies with antidepressants are biased by the generalization that antidepressants lack a specific property when the study involved only one. Antidepressants are highly specific and humans remarkably variable.
Developing a vaccine for pandemic influenza has the disadvantage of needing to know the strain of the virus, which may mutate from preparation to use. That problem would not exist with immunostimulants: once stimulated, an immune system should be effective towards all strains. The disadvantage with antidepressants as immunostimulants is matching drug to human: sertraline might be effective for one person, fluoxetine for another. Another advantage of immunostimulation would be its value in coinfection. Resistant tuberculosis, malaria and HIV are a common coinfection in the third world. Imagine the good that a daily dose of a generic antidepressant could do, along with its paltry cost.
Impaired immune function has been demonstrated in depression and stimulation of immune function by antidepressants. As lithium and antidepressants have immunostimulating properties, they are effective against a wide range of microbes. Response of infection to lithium and antidepressants mirrors that of response to depression, with subjects responding selectively to one or other antidepressant or to lithium. Antidepressants are highly specific and humans remarkably variable. When infection accompanies depression their response to lithium or an antidepressant is invariably simultaneous, suggesting that the actions of the drugs on the brain in infection are essential. Tolerance may complicate the treatment of depression, and paradoxical reactions induce or intensify symptoms. Antidepressants are, paradoxically, capable of activating dormant viruses. Elevation of mood and energy in subjects treated for tuberculosis ushered in the pharmacological treatment of depression. The wheel will turn full circle when lithium and antidepressants are integrated into the pharmacology and therapeutics of infection (4).
Lithium Builds Gray Matter In Bipolar BrainsScienceDaily (Apr. 12, 2007) Neuroscientists at UCLA have shown that lithium, long the standard treatment for bipolar disorder, increases the amount of gray matter in the brains of patients with the illness.
See also:
Health & Medicine* Psychology Research
* Nervous System
* Brain TumorMind & Brain
* Depression
* Neuroscience
* Bipolar DisorderReference
* Psychopharmacology
* Occupational therapy
* Psychosis
* Biological psychiatryCarrie Bearden, a clinical neuropsychologist and assistant professor of psychiatry at UCLA, and Paul Thompson, associate professor of neurology at the UCLA Laboratory of NeuroImaging, used a novel method of three-dimensional magnetic resonance imaging (MRI) to map the entire surface of the brain in people diagnosed with bipolar disorder.
When the researchers compared the brains of bipolar patients on lithium with those of people without the disorder and those of bipolar patients not on lithium, they found that the volume of gray matter in the brains of those on lithium was as much as 15 percent higher in areas that are critical for attention and controlling emotions.
The neurobiological underpinnings of bipolar disorder an illness marked by a roller coaster of emotions between mania and depression are not well understood. Nor is it understood how lithium works in controlling these severe mood swings, even though it has been the standard treatment for some 50 years. These new findings suggest that lithium may work by increasing the amount of gray matter in particular brain areas, which in turn suggests that existing gray matter in these regions of bipolar brains may be underused or dysfunctional.
This is the first time researchers were able to look at specific regions of the brain that may be affected by lithium treatment in living human subjects, said Bearden. "We used a novel method for brain imaging analysis that is exquisitely sensitive to subtle differences in brain structure," she said. "This type of imaging has not been used before to study bipolar patients. We also revealed how commonly used medications affect the bipolar brain."
Although other studies have measured increases in the overall volume of the brain, Bearden said, this imaging method allowed the researchers to see exactly which brain regions were affected by lithium.
"Bipolar patients who were taking lithium had a striking increase in gray matter in the cingulate and paralimbic regions of the brain," she said. "These regions regulate attention, motivation and emotion, which are profoundly affected in bipolar illness."
While conventional MRI studies have measured brain volume in total, this new image analysis allows researchers to examine differences in cortical anatomy at a much greater spatial resolution.
In this study, Bearden and colleagues at UCLA used computer analysis to analyze brain scans collected by collaborators at the University of Pittsburgh in order to determine whether bipolar patients showed changes in brain tissue and, if so, whether those changes were influenced by lithium treatment. Specifically, they employed high-resolution MRI and cortical pattern-matching methods to map gray matter differences in 28 adults with bipolar disorder 70 percent of whom were lithium-treated and 28 healthy control subjects. Detailed spatial analyses of gray matter distribution were conducted by measuring local volumes of gray matter at thousands of locations in the brain.
While the brains of lithium-treated bipolar patients did not differ from those of the control subjects in total white-matter volume, their overall gray-matter volume was significantly higher, sometimes by as much as 15 percent.
Unfortunately, said Bearden, there is no evidence that the increase in gray matter persists if lithium treatment is discontinued. "But it does suggest that lithium can have dramatic effects on gray matter in the brain," she said. "This may be an important clue as to how and why it works."
The research is featured in the July issue of the journal Biological Psychiatry. Other authors in the study included Manish Dalwani, Kiralee M. Hayashi, Agatha D. Lee, Mark Nicoletti, Michael Trakhtenbroit, David C. Glahn, Paolo Brambilla, Roberto B. Sassi, Alan G. Mallinger, Ellen Frank, David J. Kupfer, and Jair C. Soares.
Lithium Promotes the
Formation of New Brain Cells
It can help protect against neurodegenerative
diseases, including manic depression, as well as brain injury
By Will Blockeethoven is known to have been moodywhich may be an understatement. By most accounts, he was a difficult man to be around, and the few friends he had were often sorely tested by his rude and abusive behavior. One could argue, of course, that the tragedy of his deafnesssurely one of the cruelest twists of fate in human historyjustified his moodiness, if thats the correct word for it. Well probably never know, but perhaps it was more than that. Beethoven might have been afflicted by a mood disorder, a problem that goes far beyond the garden-variety bad moods to which all of us fall prey from time to time.
Psychiatrists define mood disorders as a group of mental disorders in which disturbance of mood is accompanied by either a full or partial manic or depressive syndrome that is not due to any other mental disorder. There are many varieties of mood disorders, but what they have in common is a pathological state of mania (a kind of exaggerated and unfounded elation) or depression. By themselves, mania and depression are called unipolar disorders. If, however, the patient alternates between these two extremes of moodusually in cycles of months or years, and for no apparent reasonthe condition is called bipolar disorder, which is also known as manic-depressive illness or just manic depression.
LithiumIt Is Something in the Water
According to the Japanese authors of a recent literature review (from which most of the information in this article is taken), bipolar disorder is one of the most common (35% worldwide), chronic, recurrent (90%), life-threatening psychiatric diseases (the threat comes from the tendency to suicide).1 The traditional treatment for both elements of this disorder (mania and depression) has been with lithium, a metallic element found primarily in the alkaline waters of many mineral springs and in certain dry lakes, such as Californias Searles Lake in the Mojave Desert.
For thousands of years before anyone knew about lithium, people throughout the world had been taking the waters at mineral springs, such as those in Baden-Baden, Germany. Bathing in these hot springs made people feel better, but drinking the water probably helped even more, by providing lithium in much greater amounts than are normally found in food.
Three Surprising Discoveries
Now that we know what it is in these waters that helps alleviate mood disorders, the question is: how does lithium work? To gain some insight on this, we need to be aware of three surprising discoveries made during the past decade.1
Mood disorders entail brain damage
Mood disorders are not just neurochemical in nature, i.e., they are not just attributable to simple imbalances in brain chemistry. Instead, they are now considered to be systemic diseases that entail multiple abnormalities in such areas as cognitive, motor, nervous, and endocrine functions and in the sleep/wake cycle. These dysfunctions are the result of impairments of complex biochemical signaling pathways having to do with both cell survival and cell death, and such impairments can culminate in both functional and structural abnormalities in the neurons themselves. In other words, the mood disorders entail actual brain damage, which is typically manifested as a loss of gray matter and as reductions in the number and size of neurons and glia (nonneuronal brain cells) in certain regions of the brain.Lithiums ability to stimulate neuro-
genesis is important because impaired
neurogenesis is the common, unifying
factor in the origin of various
neurodegenerative diseases.Lithium protects against multiple types of brain damage
Antidepressants, including lithium, can protect against, and may even reverse, the functional and structural abnormalities in the brains neurons. It has become increasingly evident that lithium, in particular, has neuroprotective effects against cell injuries caused by a strikingly wide variety of factors, including ischemia (inadequate blood supply), amyloid-beta (the protein constituting senile plaques in Alzheimers disease), irradiation, heat shock, and a number of different kinds of neurotoxins. The protective effects occur not just in laboratory cell cultures, but also in animals with a variety of neurodegenerative diseases and in human patients with bipolar disorder (which has come to be regarded as a neurodegenerative disease itself).The brain produces new neurons throughout life
Contrary to the long-standing belief that no new neurons are ever formed in the brain after it has fully matured (at around the age of 20), this does occur throughout our entire adult lifetime. The process, called neurogenesis, occurs primarily in the hippocampus, the region of the brain most closely associated with learning and memory. Apparently, however, neurogenesis does not occur at a rate sufficient to offset certain pathological processes that cause a loss of neurons (as occurs most strikingly in Alzheimers disease). This suggests that either increased cell death or decreased neurogenesis (or both) is associated with mood disorders. And mood disorders, as we have seen, can be prevented or treated with antidepressants.Mood Disorders Are Neurodegenerative Diseases
Taken together, these discoveries suggest that mood disorders are a novel class of neurodegenerative diseases, i.e., they may be the manifestations of chronic brain damage, in the same sense in which such diseases as Alzheimers and Parkinsons are. There is, however, an important difference between these diseases and mood disorders: the former cannot be cured, whereas the latter often can be. Thus there must be something fundamentally different about the types of brain damage involved. (The progress of Alzheimers disease can be slowed down and sometimes temporarily reversed, notably by galantamine, but the final outcome remains inevitable; there is, as yet, no cure in sight.)
Lithium Promotes Neurogenesis
It turns out that lithium increases or decreases the production of a wide variety of substances in our cells, and it interacts with a multitude of cell-survival and cell-death signaling pathways, with the overall result of enhancing the survival of existing cells and promoting the formation of new ones (neurogenesis). A recent study by a research team at Wayne State University School of Medicine in Detroit showed that administration of lithium to manic-depressive patients increased the volume of their gray matter by 3%, on average.2* The same team also showed that lithium increased the levels of N-acetyl aspartate, an indicator of neuronal viability and function.3 Referring to these studies, the authors of the above-cited review stated,1
These exciting results unveil that in human patient brains, brain atrophy is reversible, and neurogenesis may be promoted by pharmacological strategies. In addition to its current use in manic-depressive illness, it has been proposed that lithium could be used to treat acute brain injuries (e.g., ischemia) and chronic progressive inexorable neurodegenerative diseases (e.g., Alzheimers disease, Parkinsons disease, tauopathies, and Huntingtons disease).
*For more details on this and on various other specific effects of lithium, see Can Lithium Benefit Brain Health? in the June 2004 issue. And for a recent article on the benefits of galantamine in overcoming neuronal damage similar to that of Alzheimers disease, see Galantamine Aids Recovery from Brain Damage in the August 2005 issue.
Tauopathies are a diverse category of neurodegenerative diseases, of which Alzheimers is the most important (Parkinsons and Huntingtons are not tauopathies). To learn more about these diseases, see the sidebar When Bad Things Happen to Good Proteins.
When Bad Things Happen to Good Proteins
Tau (rhymes with wow) is the 19th letter of the Greek alphabet. Its also the name of an elementary particle, and its the name of a protein that serves a vital function in our neurons. Tau (τ) is associated with other proteins called tubulins in the formation and stabilization of important cellular components called microtubules. As the name implies, these are tiny, cylindrical, hollow structures (their diameter is 22 nanometers, or 22 billionths of a meter). They act not only as structural elements of the cells architecture but also as conduits for various materials, such as neurotransmitters and bits of cellular debris, that must be shuttled from one part of the cell to another.* Some microtubules are also involved in cellular locomotion, such as the swimming action of sperm cells.
*Paradoxically, these materials dont travel through the microtubules, but on them. Driven by chemical energy provided by cellular ATP molecules, and guided by exquisitely coordinated intermolecular forces, they walk along the outer surface of the microtubule until they reach their destination, which may be an enormous distance away, relatively speaking.
The trouble with tau is that its vulnerable to a biochemical process called hyperphosphorylation, which means the attachment of an excessive number of phosphate groups (OPO32) to its molecular structure. When this occurs, the hyperphosphorylated tau molecules become disengaged from the tubulin molecules, causing destabilization and collapse of the microtubules. This compromises the neurons ability to function properly, and it may die as a result.
But thats only part of the story. Once free of the tubulins, the hyperphosphorylated taus self-aggregate in the form of paired helical filaments, which tend to get tangled up with other such pairs. The resulting superaggregates, which can be seen under the microscope, are called neurofibrillary tangles; theyre one-half of the dreaded team of plaques and tangles that degrade, and ultimately destroy, significant portions of the brains of Alzheimers victims. (The plaques are extracellular, whereas the tangles are intracellular.)
Surprisingly, recent experiments with transgenic mice have suggested that neurofibrillary tangles do not necessarily cause neuronal death, as had long been believed, and that the processes leading to their formation are not necessarily related to those that cause memory loss and other forms of cognitive impairment. For a discussion of this work, see the sidebar Stunning News Regarding Alzheimers Disease in the article Galantamine Can Modify Alzheimers Disease in the October 2005 issue.
Alzheimers is the most important example of a tauopathy (pronounced tau-AW-pathy), a neurodegenerative disease characterized at least in part by a pathology involving tau. Various factors are implicated in the formation of neurofibrillary tangles, but one is particularly noteworthy: its amyloid-beta, the deleterious protein that forms the core of the senile plaques in Alzheimers. Thus, the plaques help spawn the tangles, which explains why the latter usually appear later in the course of the disease than the former.
The distribution of neurofibrillary tangles within the brain also changes with time. It starts mainly in the entorhinal cortex, a region from which bundles of cholinergic neurons project to the hippocampus, the most critical region for learning and memory. Over time, tangles then make their appearance in the hippocampus itself and in nearby regions of the cerebral cortex, and they eventually spread throughout the cortex.
Aside from Alzheimers disease, the other 20-plus tauopathies are not well known to laymenwith one exception. Physicians call it dementia pugilistica, but we know it better as being punch drunk. Boxers who take too many blows to the head suffer from a tau-related dementia that closely resembles Alzheimers disease, including the presence of abundant plaque deposits. It appears that both diseases share common pathogenic mechanisms leading to the formation of plaques and tangles.1 This idea jibes with the fact that head trauma is a known risk factor for Alzheimers.
Reference
1. Tokuda T, Ikeda S, Yanagisawa N, Ihara Y, Glenner GG. Re-examination of ex-boxers brains using immunohistochemistry with antibodies to amyloid beta-protein and tau protein. Acta Neuropathol (Berlin) 1991;82:280-5.
Impairment of Neurogenesis Underlies Neurodegenerative Disease
Lithiums ability to stimulate neurogenesis is exceptionally important because, according to some scholars, the impairment of neurogenesis is the common, unifying factor in the origin of various neurodegenerative diseases, including both tauopathies and non-tauopathies. Although the clinical symptoms and neuropathological abnormalities exhibited by these diseases are distinct in each case, they overlap one another to form a continuous spectrum, suggesting that common threads may run through them all.
Factors that tend to promote neurogenesis include: task-learning; an enriched environment (i.e., one that contains abundant sensory stimuli and mental challenges); physical exercise; various growth factors (substances that promote the growth and development of tissues); various neurotransmitters (e.g., serotonin, dopamine, and noradrenaline); various hormones (e.g., estrogen and DHEA); and antidepressants, such as lithium. A study published in 2003 provided the first direct evidence that the behavioral improvements seen with antidepressants are caused in part by the neurogenesis they induce.4
Lithium Combats Both Plaques and Tangles
Meanwhile, much experimental evidence has accumulated showing that lithium inhibits the production of amyloid-beta and the hyperphosphorylation of tau, apparently by inhibiting the actions of two enzymes, GSK-3α and GSK-3β (GSK stands for glycogen synthase kinase), that are involved in these processes.5 Lithium thus shows promise for combating both plaques and tangles, the two most destructive agents in the brains of Alzheimers victims. Experiments have also shown that lithium has potential benefits (as mentioned in the quotation given above) for the treatment of other tauopathies and for Parkinsons and Huntingtons diseases, as well as for brain injury caused by ischemia.
Taking the Lead Is Good, Unless . . .
Although we dont know whether Beethoven suffered from a true mood disorder of neurological origin, we do know that he died, at age 57, from severe, chronic lead poisoning. This was proved in 2005 by scientists at the Argonne National Laboratory, near Chicago, who analyzed authenticated skull and hair samples from the great composer. (They also debunked the long-standing belief that Beethoven had syphilis. The antisyphilitic drugs of his time contained mercury, traces of which would have been detectable in his remainsbut none were found.)
Scientific evidence reveals that Beethovens poisoning began no later than his early twenties. It probably accounted for the many illnesses and the chronic pain he suffered throughout his adult life, all of which surely contributed to his bad moods. How the poisoning came about is unknown, but Vienna in his time did have a large lead-manufacturing industry. It has also been speculated that his first serious exposure to lead may have occurred accidentally when, at the age of 16, he visited the famed spa at Baden-Baden, whose mood-healing waters owed their efficacy to lithium.
References
1. Wada A, Yokoo H, Yanagita T, Kobayashi H. Lithium: potential therapeutics against acute brain injuries and chronic neurodegenerative diseases. J Pharmacol Sci 2005;99:307-21.
2. Moore GJ, Bebchuk JM, Wilds IB, Chen G, Manji HK. Lithium-induced increase in human brain grey matter. Lancet 2000;356(9237):1241-2. Erratum: Lancet 2000;356(9247):2104.
3. Moore GJ, Bebchuk JM, Hasanat K, Chen G, Seraji-Bozorgzad N, Wilds IB, Faulk MW, Koch S, Jolkovsky L, Manji HK. Lithium increases N-acetyl-aspartate in the human brain: in vivo evidence in support of bcl-2s neurotrophic effects? Biol Psychiatry 2000;48:1-8.
4. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 2003;301:805-9.
5. Alvarez G, Muñoz-Montano JR, Satrústegui J, Avila J, Bogónez E, Díaz-Nido J. Regulation of tau phosphorylation and protection against β-amyloid-induced neurodegeneration by lithium. Possible implications for Alzheimers disease. Bipolar Disord 2002;4:153-65.
Drug commonly used to treat bipolar disorder may increase lifespan
Wed, 10/31/2007 - 01:09 - NLNNematode worms treated with lithium show a 46 percent increase in lifespan, raising the tantalizing question of whether humans taking the mood affecting drug are also taking an anti-aging medication.
Results of the Buck Institute study, led by faculty member Gordon J. Lithgow, PhD, are currently published online in the Journal of Biological Chemistry.Lithium has been used to treat mood affective disorders, including bipolar disease for decades. While the drug has been shown to protect neurons, the underlying mechanism of its therapeutic action is not understood. In humans, lithiums therapeutic range is very limited and the drug has serious side effects. The research provides a novel genetic approach to understanding how lithium works and highlights the utility of using the nematode C. elegans as a research subject in the field of pharmacogenetics. Pharmocogenetics involves the study of genetic factors that influence an organisms reaction to a drug.
In the study, scientists discovered that longevity was increased in the worms when the lithium turned down the activity of a gene that modulates the basic structure of chromosomes.
Lithgow believes that lithium impacts many genes. Understanding the genetic impact of lithium may allow us to engineer a therapy that has the same lifespan extending benefits, said Lithgow. One of the larger questions is whether the lifespan extending benefits of the drug are directly related to the fact that lithium protects neurons. The process of normal aging in humans is intrinsically linked to the onset of neurodegenerative disease. However, the cellular changes and events due to aging that impact neurodegeneration are not yet understood said Lithgow. Studies involving compounds such as lithium could provide breakthroughs in the attempt to understand the biomedical link between aging and disease. Lithgow and his lab are now surveying tens of thousands of compounds for affects on aging.
The study highlights the efficacy of using C. elegans as a new way of studying drug toxicity and genetic impacts of compounds currently in drug development or already in use in humans. The use of simple model organisms with well developed genetic tools can speed the identification of molecular targets, said Lithgow. This could facilitate the development of improved therapies for diseases.
Lithium is no miracle drug. Most likely it will benefit you and many others at a low dose. Whether or not it is the answer to your problems is up to you to find out of course. I think the problems with lithium that you are concerned about are more likely with the higher doses that are used to take bipolars out of severe episodes of mania.Yes I do think you could benefit from a lower dose of lithium. I also think that you could lower it after being stabilized for a while on a higher dose. I know of a few people that have been able to do this.
I am currently taking lithium, other than being dehydrated, I haven't noticed any side effects. I am on 600 mgs and have only been on this for a month or so. My case is going to be tough treat, I may be better off taking depakote and lithium together at lower doses. This combination has great potential for neuroprotection.
Lithium: How Good is it?Many people worry that lithium is one of psychiatry's "Big Guns", something we use for patients with really severe mental illnesses. They think, "Hey, I'm not that sick", and conclude that lithium is not right for them.
They don't know that lithium, in lower doses, is used in plain depression (not bipolar, not severe). In fact, for depression that hasn't fully responded to an antidepressant, one research group calls it "Step 1A" -- the thing to do, in some cases, before switching to another antidepressant.
But one of the strongest arguments for lithium is the way it appears to protect neurons. So I wanted to show you the world's expert on how lithium works, talking about this aspect of lithium's potential benefits. His full comments, on a range of topics, from his interview with a great bipolar advocacy organization, can be read on this link at the Child and Adolescent Bipolar Foundation (CABF).
Here are Dr. Manji's comments about lithium (it's a little technical; look for the few ideas I put in bold if you're getting bogged down):
CABF: Speaking of lithium, your research has uncovered some of its intriguing beneficial properties. Can you highlight the most important ones?
MANJI: Many of the genes that are considered neuroprotective [keep brain cells from dying when stressed] are being remarkably turned on by lithium. Is lithium actually neuroprotective? We hadn't thought this way before. A number of studies have taken animal cells and tried to kill them by causing stroke, etc. These studies have consistently shown that lithium, if administered before you try to do the bad things (such as induce a stroke), protects the animal's neurons. In lithium-treated brains, the size of the resulting stroke is smaller, the number of neurons that die is lower, etc. That was amazing. Since these studies were done in rats, you need to be careful about jumping to conclusions that lithium is neuroprotective in people.
Wayne Drevets' group published a finding in Nature about five years ago that in a part of the pre-frontal cortex of bipolar patients or patients with familial recurring unipolar depression, there was almost a 40% reduction in the amount of gray matter. That was a remarkable finding that you have such a reduction in a discrete part of brain. We spoke to him about our lithium findings and asked him to reanalyze the data. He had a small group of patients who had been treated with lithium for a long time and they did not show the brain atrophy compared with the bipolar patients. Interestingly all of the patients with unipolar depression, whether or not they had been treated with antidepressants, still showed the atrophy. That was a suggestion that bipolar treatments might have a protective effect.
Valproate (Depakote) in the prefrontal cortex seemed to have the same type of neuroprotective properties. Lithium and depakote do not have identical effects in every brain area, but in this area they did. Brains treated with chronic lithium or valproate seemed not to have the atrophy in the prefrontal cortex. But it was a very small sample and a crossectional study [type of study whose design restricts its findings to association between variables, not proof of cause]. He studied them once. We don't know if it was a cause or effect. Is it the people who don't have the atrophy who responded to the drug in the first place?
We did some studies taking bipolar patients off their meds -- they were referred to us because their treatments weren't working. In every case, they either hadn't been on lithium or had been on lithium sparingly -- had started on it, had side effects, switched, and the new med was not working. These are bipolar depressed patients. We did MRI scans and MRS spectroscopy and then put them on lithium in a blinded fashion for 4-6 weeks. Then we did the scans again. We found that almost every single person taking lithium had an increase in N-acetylaspartic acid (NAA) [an amino acid that is viewed as a marker of neuronal health]. And the actual amount of gray matter was going up when they were treated chronically with lithium. This study was done together with Dr. Greg Moore¹. This was happening in areas of the patients' brains that had been atrophied. The increase was not due to swelling from water retention. The increase was seen only in areas where the brain matter had previously atrophied.
Our working hypothesis, and I think it is reasonable, is that lithium is turning on some of these growth signaling pathways and reversing the damage. It seems that the cells are shrunken, not dead, and are capable of going back to their normal sizes and sending normal projections. What lithium seems to be doing is turning on the signaling pathways that produce growth factors in the brain, such as brain-derived neurotrophic factor (BDNF), and where you have atrophy, turning on this pathway seems to be capable of reversing it. And that is a remarkable finding.
A couple of other studies since then have compared lithium-treated patients with untreated patients. They showed that the lithium-treated patients have the increase in gray matter, suggesting that lithium is causing the increase. If that is the case, lithium has a neurotrophic [nourishing to neurons] effect. Would lithium, then, be beneficial in any bipolar patient, even if he or she can't tolerate it or if his or her symptoms respond better to another mood stabilizer? One question is tolerability. We've done a number of animal studies with low-dose lithium. We found that in animals, with a dose of lithium that is one-half or one-third of a usual dose, you still get a large increase in bcl-2, a neuroprotective protein. This suggests that it is quite possible that even low-dose lithium will exert these effects. Many studies are being planned using low-dose lithium as an additional agent in patients being treated with something else. We will add low-dose lithium and follow them for 2-3 years with repeated MRIs and neuropsych testing to see if the addition would be enough to provide neuroprotective effects that would help them long-term with the illness, even if something else is their appropriate treatment for symptoms. That is extremely important. It is a devastating long-term illness, and brain atrophy may be responsible for that. If we can intervene early on and prevent that, there is reason to believe you will have a big impact on the overall course of the illness.
I think the key is to keep these medications low if you can. Then you will benefit from neuroprotecion and other things without compromising your health
Posted by morganpmiller on June 18, 2009, at 3:09:59
In reply to Re: How would you medicate this? thanks to all for, posted by morganpmiller on June 18, 2009, at 3:05:16
You may want to consider a low dose combo of lithium and valproate. Evidently they may works synergistically in neuroprotection/mood stabilization. If a low dose works for you, maybe along with an antidepressant, you most likely will not have to worry about the toxic effects of either lithium or valproate. Start of with a low dose of lithium and then add valproate at a low dose if lithium alone is not enough. Worth a try and you won't have to worry too much about toxic effects. Talk your doc about it.
Posted by morganpmiller on June 18, 2009, at 3:22:30
In reply to How would you medicate this?, posted by Maoiman on June 16, 2009, at 15:59:39
One more thing, sounds like you are bipolar. You have to consider that bipolar is mostly a predisposition for many. There are factors like childhood environment and other life stressors that are at the root of and triggers for your depression. That said, I would seriously consider seeing a really good therapist, preferably one that has a phd and uses a psychodynamic philosophy. I would also find a good open minded psychiatrist. Remember, most mental illnesses are of bio-psycho-social origin. We can't go through life blaming everything on our biology. If we do, we may never truly get better. Therapy is not easy. Expect to feel worse before you get better. No pain no gain. God I hate that I said that but in this case it is true unfortunately. I know, it sounds cruel. You would think that after already suffering you should not have to suffer anymore in order to get better. I guess that is why you take to medication and hopefully are surrounded by support so you can be strong enough to work through the difficult issues.
Posted by Maoiman on June 18, 2009, at 12:25:32
In reply to Re: How would you medicate this?, posted by morganpmiller on June 18, 2009, at 3:22:30
Many thanks for these very informative posts,It is much apreciated. I think I'll give the Lithium a try soon, , would be so nice to feel settled down in myself.Cheers
MM
Posted by morganpmiller on June 18, 2009, at 23:07:37
In reply to Re: How would you medicate this?, posted by Maoiman on June 18, 2009, at 12:25:32
Hopefully you feel good enough soon to also benefit from intense exercise, yoga, and other physical activities that may help. Always spend a while sretching after working out, stretching increases levels of GABA, the calming neurotransmitter. I know its hard to do all these things when you feel like sh*t. Hope you find the right medication treatment soon so you can start living your life again. Good luck
Posted by desolationrower on June 19, 2009, at 9:02:13
In reply to Re: How would you medicate this? thanks to all for, posted by morganpmiller on June 18, 2009, at 3:09:59
you have pretty much the classic case of someone who should be taking lithium
-d/r
Posted by morganpmiller on June 20, 2009, at 1:27:00
In reply to Re: How would you medicate this? thanks to all for, posted by desolationrower on June 19, 2009, at 9:02:13
> you have pretty much the classic case of someone who should be taking lithium
>
> -d/rYour talking about me right? Or the OP?
Posted by desolationrower on June 20, 2009, at 1:40:01
In reply to Re: How would you medicate this? thanks to all for, posted by morganpmiller on June 20, 2009, at 1:27:00
oh i mean the op
-d/r
This is the end of the thread.
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