Agitated Exhaustion and Hypomania

Discussion in 'Fibromyalgia Main Forum' started by Slayadragon, Feb 19, 2007.

  1. Slayadragon

    Slayadragon New Member

    louisek asked me about this in another post, but I thought it would be good to label it for more general interest.

    Note that I originally mentioned this concept in comparing it to mild hypomanias (particularly those called "mixed states") that those with manic-depression sometimes experience.

    This may be especially relevant because:

    * At least according to the info in Osler's Web, manic-depressives and CFS patients are pretty much the only people who have the unidentified bright objects on MRI's of their brains.

    * Many manic-depressives seem to suffer from seizures of those parts of the brain that control emotions. Anti-convulsants such as Lamictal and Depakote control the disease successfully in many cases. One of my doctors (Morris Papernik) told me recently that Lamictal has had some success in treating the agitated exhaustion of CFS as well.

    * Many people believe that Klonopin and Xanax seem useful for controlling agitated exhaustion of CFS because of their anti-seizure activity. Other benzodiazapines apparently a) do not have as much anti-seizure activity and b) are not as helpful to CFS sufferers.

    * Both manic-depression and CFS often are preceded by head injuries.

    I don't know quite what to make of this information. It does seem that there is a weird relationship between CFS and manic-depression, though.

    For what it's worth, I've had very mild mood swings since adolescence (and have a strong family history of depression and mild manic-depression). My mood swings were exacerbated by a head injury (and now are controlled with Lamictal). The CFS followed the head injury by about a year.

    I'm interested in theories about this topic. I haven't seen nearly enough on it.

    Meanwhile, here is some information on the topic of "agitated exhaustion." It comes from the book "Chronic Fatigue Syndrome: A Treatment Guide" by Erica Verrillo and Lauren Gellman.

    This book is a decade old, but I highly recommend it anyway. It lists pretty much every weird symptom associated with CFS and attempts to give explanations for them (based on interviews with CFS experts). I've not found any other book or information source about CFS that does this nearly as well.

    Best, Lisa


    Agitated Exhaustion

    The term "agitated exhaustion" is used by Dr. David Bell in his book, "The Doctor's Guide to Chronic Fatigue Syndrome," to characterize the type of fatigue typical of the acute stage of CFIDS and it describes very well the inability to "turn off" that the severely ill suffer.

    It is often described as a "tired and wired" feeling. A person with this type of fatigue does not feel sleepy, although the desire for rest is overwhelming.

    This type of exhaustion is usually accompanied by insomnia and catecholamine-related symptoms such as rapid pulse, hyperventilation, panic, and loss of appetite. The cause of this type of fatigue is thought to be neurologic.

    Dr. Paul Cheney puts forth a possible explanation for many of the neurologic upsets experienced in CFIDS (CFIDS Chronicle, Spring 1995). He proposes that toxins that accumulate in the brain as a result of cell dysfunction, liver toxicity, or excess cytokine production can lead to alterations in the normal firing pattern of the brain, resulting in a state of sustained neuronal arousal.

    In the state that Dr. Cheney describes, even small stimuli spark strong responses from the nervous system. The continued state of arousal characteristic of acute and severe CFIDS results in agitated exhaustion.

    Dr. Cheney points out that nearly every treatment that slows nervous system responsiveness aids in controlling neurologic symptoms, including benzodiazepines (Klonopin), magnesium, taurine, nimodipine (Nimotop), melatonin, calcium channel blockers, butyric acid (Butyrex), and gamma-aminobutyric acid (GABA). Meditation, hypnosis, acpuncture and biofeedback can also provide help.

  2. LouiseK

    LouiseK New Member

    Thank you so much for the post. I HAVE this. No depression but I have those white spots on MRI and along with the illness came this intense agitation. If I am alone and quiet I don't get it. I work so hard to get myself sort of "wound up" if you get my drift when I have to go out or when I used to work or even now when I am with people. It seems once I wind up to do what I need to do it just gets out of control. If I am active in the evening I cannot sleep all night.

    It was horrible at work because I was claiming to be sick but when I did get to the office I was like a live wire. I couldn't help it.

    Just another one of the emotionally charged aspects of all this -- not only do you not "look sick" but I am running all about and chattering nervously.

    I am going to look further into this. Your post was intensly interesting to me and, you know, these things comfort somehow.

  3. swedeboy

    swedeboy Member

    I don't think I am bi-polar but I can really relate to the agitated exhaustion and tired but wired feelings, accompanied with overwhelming anxiety. Are there any suggestions on how I can convince my GP doctor to prescribe the correct meds like benzodiazepines, etc.

    My GP doctor seems to think anti-depressants (desipramine), flexeril and ambien are all she can do for me. FLexeril works a bit for the tired but wired feelings, but my doctor prescribed it for pain. Ambien makes my depression worse so I rarely take it. and Dr. Montoya will not address any of these symptoms.

    Eventhough I live in the heart of technology (the Silicon Valley) there are no CFS specialists here. My county (santa clara county) has the highest income per capita in the entire state and it has the tenth largest city in the country; San Jose which also has the lowest crime of any city with a population over 100,000. Location, Location Location! So why do no CFS specialists set up practist here? I just don't understand it.

    The closest CFS specialist is Dr. Peterson 200 miles away.
    And even if I see Dr. Peterson there is no guarentee that my GP doctor will follow Dr. Petersons suggestions for treatment. I go see Dr. Montoya on Feb.27th, and I hope and pray that his anti-viral treatments will help me.

    Thanks for sharing your story and info Lisa!

    Peace and Love, Swedeboy
  4. Slayadragon

    Slayadragon New Member

    I don't know what kind of approach your internist has toward her patients, but if she's open-minded you could bring in the book mentioned above and show it to her.

    In addition to the part quoted above, there are three pages in the "Prescription Drugs" section on benzos.

    Since only a small amount of Klonopin is needed in order to get good sleep (and since your doctor knows you're proactively trying to get your illness treated in every way possible), perhaps she would be willing to let you give the drug a try. At least a few other people on the board have done this successfully with ordinary primary care physicians.

    I'm putting an article on Klonopin from the library of this board in the post below.

    Good luck with your appointment with Dr. Montoya, of course.

    Best, Lisa

  5. Slayadragon

    Slayadragon New Member

    Dr. Paul Cheney Discusses the Benefits of klonopin
    by Carol Sieverling


    Editor’s Note: The following is based on a recent interview conducted by Carol Sieverling with Dr. Paul R. Cheney, M.D., Ph.D., and the article "CFIDS Treatment: The Cheney Clinic’s Strategic Approach" (CFIDS Chronicle, Spring 1995). Dr. Cheney gave permission to share this information, but has not reviewed or edited it.

    Many CFIDS specialists prescribe the drug klonopin. In the October 1999 issue of The Fibromyalgia Network, nine CFS/FM specialists summarized their most effective treatments, and six included klonopin. Interestingly, the three who did not are primarily FM specialists.

    Dr. Cheney prescribes klonopin to address a condition associated with CFIDS called "excitatory neurotoxicity." To explain this condition to patients, he draws a line with "seizure" on the far left and "coma" on the far right. A big dot in the middle represents where healthy people are when awake. A dot somewhat to the right of the middle indicates where healthy people are when asleep – slightly shifted toward coma. He highlights in red the left portion of the line, from seizure to the middle, and labels it "Neurotoxic State" (damaging to the brain). He highlights in blue the right portion of the line, from coma to the middle, and labels it "Healing State."

    In CFIDS, an ongoing injury to the brain shifts patients toward seizure. A dot to the left of the middle, marked "injury," represents the position of CFIDS patients. This puts us in the red "Neurotoxic" zone. When we shift toward seizure, we often experience "sensory overload." It’s as if our brain’s "radar" is too sensitive. Our neurons (nerve cells) are sensing stimuli and firing when they should not. This causes amplification of sensory input. Light, noise, motion and pain are all magnified. At the beginning of their illness, many patients report feeling exhausted, yet also strangely "wired." The "wired" feeling is the slight shift towards seizure that occurs as a result of the excitatory neurotoxicity.

    Cheney frequently uses the term "threshold potential" when discussing excitatory neurotoxicity. (Think of the threshold - bottom - of a doorway. The lower it is, the more accessible it is. When it is at floor level, everything can enter. When it is raised, access is restricted to taller people. If it is too high, no one can enter.) Threshold potential refers to how much stimulus it takes to make neurons fire. If the threshold potential is too low, even slight stimulation is "allowed to enter" and is detected by the neurons. This causes the neurons to fire, resulting in sensory overload. If the threshold is dropped to nothing, all stimuli get through and the neurons fire continuously, resulting in a seizure. If the threshold is raised, only stronger stimuli can make neurons fire. A healthy person’s threshold potential naturally rises at bedtime, promoting sleep. If the threshold potential is too high, you feel drugged or drowsy. If the threshold potential is raised extremely high, coma results.

    Two receptors in the brain, NMDA and GABA, determine the threshold potential. During the waking hours of a healthy person, NMDA and GABA should be equally active. This balances the person in the middle of the seizure/coma continuum. NMDA stimulates, and GABA inhibits. If NMDA increases, one moves toward seizure. If GABA increases, one moves toward coma.

    In CFIDS, NMDA is more activated than GABA, lowering the threshold potential. This causes neurons to fire with very little stimulation, resulting in sensory overload. This condition of excitatory neurotoxicity is dangerous. Dr. Cheney emphasizes that in an attempt to protect itself, the body will eventually kill neurons that fire excessively. He states that brain cell loss can result if this condition isn’t addressed.

    How can the brain be protected against excitatory neurotoxicity? klonopin. This long acting benzodiazepine has been Dr. Cheney’s most effective drug for CFIDS over the years. He believes that klonopin and the supplement magnesium may be two of the most important treatments for CFIDS patients because of their neuroprotective qualities. He recommends two or more 0.5 mg tablets of klonopin at night. Paradoxically, very small doses (usually a quarter to a half a tablet) in the morning and mid-afternoon improve cognitive function and energy. If the daytime dose is low enough, you’ll experience greater clarity and think better. If the daytime dose is too high, you’ll become drowsy. Adjust your dose for maximum benefit, taking as much as possible without drowsiness. Adjust the morning dose first, then take the same amount mid-afternoon if needed, then take three to four times the morning dose at bedtime. Dr. Cheney recommends doubling the dose during severe relapses.

    Dr. Cheney most frequently prescribes the combination of klonopin and Doxepin, along with the supplement "Magnesium Glycinate Forte." Magnesium Glycinate alone is a good choice for the more budget minded( sells it as "Magnesium Plus".) A common dosage of magnesium is 200 mgs at bedtime. Too much magnesium can cause diarrhea, though glycinate is usually the best tolerated form.

    Cheney prescribes Doxepin in the form of a commercial elixir (10mg/ml). At low doses, this tricyclic antidepressant acts as a very potent antihistamine and immune modulator. Doxepin acts synergistically with klonopin to assist sleep, and may improve pain. Patients tend to be very sensitive to Doxepin, which can cause morning fog and fatigue if the dose is too high (5 to 10 mg or higher). He recommends starting at two drops a night and gradually increasing the dose until "morning fog" becomes a problem. Most patients can’t tolerate more than half a cc.

    On a handout entitled "Neuroprotection via Threshold Potentials," Cheney lists six substances that can protect the brain. Under the category "NMDA Blockers" Cheney lists:

    1. Parenteral magnesium and taurine (intramuscular injections of magnesium and taurine, usually given with procaine) 2. Histamine blockers (Doxepin Elixir) Under the category "GABA Agonists" (increases GABA) Cheney lists: 3. klonopin 4. Neurontin 5. Kava Kava 6. Valerian Root

    klonopin is taken "day and night"; Neurontin "night, or day and night"; kava kava “daytime only”; and valerian “nighttime only.” The first four are by prescription, the last two are herbs. In my limited experience, only certain patients are put on magnesium/taurine injections, and then only for a limited period before switching to oral supplements.

    Many myths abound concerning klonopin. When asked about these myths, Dr. Cheney shared the following information.


    When the generic Clonazepam came on the market, many patients switched to it because it was less expensive than klonopin. Cheney then began hearing that most patients had to take more Clonazepam to get the same effect. Generics aren’t exactly identical to the original products, and with most drugs the slight variations don’t matter. However, most CFIDS patients can tell the difference between klonopin and its generic form, Clonazepam. Most find klonopin to be more effective.


    Dr. Cheney was adamant that klonopin is not addictive. In treating thousands of patients, he has never seen a patient become addicted to klonopin. He reviewed the definition of addiction, stating that it involves: (1) psychosocial disruption, (2) accelerated use, (3) inappropriate use, and (4) drug seeking behavior.

    Dr. Cheney said a case might be made that klonopin is habituating. It’s true that it can’t be stopped suddenly. You must taper off of it gradually. However, he was cautious about even calling it habituating. The process of tapering off a drug is not the same thing as withdrawal, a term that implies addiction.

    Dr. Cheney said to keep in mind that klonopin is given for a physiological problem – excitatory neurotoxicity. It’s prescribed to adjust the threshold potential: to keep neurons from firing inappropriately and being destroyed. He stressed that klonopin should never be given unless you intend to raise the threshold potential. He stated, "Problems arise when you begin to use benzodiazapines for reasons other than threshold manipulation." However, CFIDS patients have a "threshold potential aberration" and need klonopin (or something similar) to avoid brain injury. Dr. Cheney has never seen a recovered patient have difficulty coming off klonopin. He stated, "When you no longer need the drug, coming off it is very easy."

    On the other hand, trouble arises when someone who still has an injured brain tries to come off klonopin. It’s like a thyroid patient stopping their thyroid medication. Dr. Cheney warned, "All hell breaks loose". However, it’s not because the drug is addicting, and it’s not withdrawal. The condition still exists, and the body lets you know it has a legitimate physical need for the drug. Cheney stated, "When a CFIDS patient who is still experiencing the underlying mechanisms of brain injury goes off klonopin, there is a burst of excess neural firing and cell death. That’s the havoc we hear about that is mistakenly called withdrawal."


    Dr. Cheney said that he honestly doesn’t understand this concern. He believes klonopin might disrupt the sleep of people who take it for conditions other than the threshold potential aberration found in CFIDS. He also acknowledged that if you are looking just for drugs to facilitate sleep, klonopin is certainly not the first one to come to mind, nor should it be used to induce sleep in "ordinary" patients. It’s not a sleep drug per se. However, a large part of the sleep disorder of CFIDS is excitatory neurotoxicity and the resulting shift toward seizure. If you treat this condition with klonopin, then you have treated a large part of the sleep disorder in CFIDS. Most importantly, he said he simply does not see stage 4 sleep disruption in his patients on klonopin.

    Towards the end of this discussion on klonopin, Cheney smiled, and remarked, "But suppose I’m wrong about the brain injury and the threshold potential aberration and the shift toward seizure? What if I’m wrong about your need for klonopin? I’m absolutely sure I’m right, but what’s the worst case scenario? Do you know what long-term studies on klonopin have shown? Reduced incidence of Alzheimer’s Disease. Alzheimer’s Disease is a complicated and convoluted way of knocking out your neurons, and klonopin protects your neurons. Now it’s believed that klonopin didn’t actually stop Alzheimer’s. It just delayed its onset so long that everyone died of something else before they ever got it - which is to say you won’t get Alzheimer’s. You’ll die of something else first."

    The last question Cheney addressed concerned the dose: what happens if the dose is too high? He said the only down side was that if you took a little too much (we are not talking overdose here) it would shift you toward coma on the continuum. It would shut your brain down to some degree, and thus impact your ability to function. This is inconvenient, but it’s not harmful. In fact, it shifts you into the "healing state" on the continuum. You may feel like a zombie, but your brain is protected and your neurons are not getting fried. However, not being able to function isn’t an option for most of us, so we need to find the maximum dose that doesn’t make us drowsy.

    Dr. Cheney emphasized that klonopin, Doxepin, and magnesium are very, very good at protecting the brain from cell death due to excess firing. However, they can’t stop the underlying mechanisms of CFIDS that are injuring the brain in the first place.

    Though it can’t stop the underlying mechanisms causing the injury, klonopin can protect your brain and keep your neurons from being destroyed. Then, as Cheney put it, "When you come out on the other side of this, you’ll have more of your brain left."

    [This Message was Edited on 02/19/2007]
  6. Forebearance

    Forebearance Member

    Wow, Swedeboy, that is shocking that there are no CFS specialists where you live!!

    I have a similar problem. It's shocking to me that there are no CFS specialists in my large town/small city.

    I was lucky to find a regular doctor who has a small ego and who believes me. If I give her some printed info or studies that show that CFS experts are doing something, she's happy to let me try it, also.

    I think the coolest thing about my doctor is that she freely admitted that she knew nothing about CFS. That made her open-minded to my ideas. Now she probably knows more about CFS than any other doc in my town, and there are two medical schools here!!! (gnashing of teeth)

    To me, the most dangerous doctor is the one who thinks s/he knows about CFS, and won't admit that s/he doesn't really understand it that well.

    But it has also taken time to create the trust and good working relationship that I have with my doc. I've been going to her for about seven years.

    I wish you had someone good to work with. Someone who wouldn't leave you feeling frustrated.

    I think I understand what you all mean by agitated exhaustion. I also have had to get myself really wound up to do things out in the world, and then it takes me hours to wind down afterwards.

    And in the early years of my illness, I used to have insomnia where I couldn't fall asleep at night. That was before I figured out all my sleep-enhancing supplements. (Calcium, magnesium, thryoid, estrogen and progesterone)

  7. spacee

    spacee Member

    I think he has a different thinking about this. Fascinating. I just watched it today and I am all hyped up about it. It describes me to a T.

    We have a friend who has worked on the house for about a year. He, at one time, wanted to be a doctor and has a degree in Biology. Then, he decided he wanted to be a general contractor.

    Anyway, I asked him to watch it with me since he understands and is very interested in science. He loved it. He, too, said that it described me exactly.

    It is extremely technical. I didn't know that Cheney's Phd is in Physics. (has his MD too). What a brilliant man.


    Oh, Yes, Dr. Cheney says that the body is taking these serotomins and dopamines, etc from the brain TO KEEP US ALIVE. And that is what causes all the extremes. Putting them in when the body is taking them away is NOT good.
  8. Slayadragon

    Slayadragon New Member

    I've never seen any evidence that the branded Klonopin is better than the generic either.

    However, after using the drug for nine years, it's my impression that some generics do work better than others, meaning that I can get as much help with my sleep even though I'm taking a lower dose.

    Does anyone happen to know which generic is the "real stuff"? If I knew, perhaps I could seek it out.

    I would prefer not to take more of this drug than is necessary to get good sleep, of course.

    Best, Lisa

  9. swedeboy

    swedeboy Member

    Lisa, Thanks for the great info, I really appreciate it. I checked out those books on Amazon. I was able to actually view inside the books.

  10. cherylsue

    cherylsue Member

    I take Tiva generic brand Clonazepam - very lose dose .25mg a few days a week. I really like it as it puts me into a deep sleep for about 5 hours. I forgot what real sleep is before this. It is the only sleep med that worked for me.

    However, I'm scared of addiction and tolerance. I tried to stop it for a few days. If I take too much I have next day sedation.

    It's controversial, but I figure at the low dose that I take, it probably is okay.

  11. Slayadragon

    Slayadragon New Member

    Thanks for your kind words.

    My Lamictal dose is on the high side--300 mg.

    The protocol for Lamictal is to start at a very low dose and then work upwards. This vastly decreases the likelihood of negative side effects.

    CFS patients (who are not very tolerant to many drugs) may want to work up even more slowly than other people.

    I think the starting dose is now 10 mg per day. Then you increase by 25 mg every week or so until moods are stabilized.

    Oddly, a lot of people seem to get a noticeable effect from Lamictal from their very first pill, even though it takes a lot of the medicine to get totally stabilized. So finding out if you're going to be helped by the drug often takes a lot less time than it would seem from the above.

    Good luck.

    Best, Lisa

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