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 Ò 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". ItÌs as if our brainÌs "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 personÌs threshold potential naturally raises 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 isnÌt addressed. How can the brain be protected against excitatory neurotoxicity? Klonopin. This long acting benzodiazepine has been 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 2 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 midafternoon if needed, then take three to four times the morning dose at bedtime. 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". (Made by Douglas Labs, it includes taurine, and is available from needs.com.) Magnesium Glycinate alone is a good choice for the more budget minded. (It's available from Needs as "Magnesium Complex" made by Klaire. Immunesupport 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 anti-depressant 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 canÌt 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 & 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 I asked Dr. Cheney about these myths, he shared the following information. MYTH NUMBER ONE: THE GENERIC IS JUST AS GOOD. 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. MYTH NUMBER TWO: KLONOPIN IS ADDICTIVE. Dr. Cheney was adamant that Klonopin is not addictive. In treating thousands of patients, Cheney 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. Cheney said a case might be made that Klonopin is habituating. It's true that it can not be stopped suddenly. You must taper off of it gradually. However, Cheney 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. Cheney said to keep in mind that Klonopin is given for a physiological problem, excitatory neurotoxicity. It is 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. 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 is like a thyroid patient stopping their thyroid medication. Cheney warned, "All hell breaks loose". However, it is not because the drug is addicting, and it is 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. ThatÌs the havoc we hear about that is mistakenly called withdrawal." MYTH NUMBER THREE: KLONOPIN DISRUPTS STAGE 4 SLEEP. Dr. Cheney said that he honestly does not 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 am 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. AlzheimerÌs 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 AlzheimerÌs. 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. (Those mechanisms are another story, and can only be explained by Dr. Cheney himself, hopefully in the video that will be made when he speaks here in the Dallas-Ft. Worth area on October 20, 2001.) 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."