Jay A. Goldstein, M.D.

This treatment protocol is a 2-years-later update from that which appeared in my most recent book, Betrayal by the Brain, published by the Haworth Medical Press in 1996. It provides physicians with little experience in CFS/FMS neuropharmacology (which is, unfortunately, almost all of them) a "cookbook" which can significantly and very rapidly improve symptoms of the large majority of patients. Physicians can use these medications much more effectively, of course, if they understand their mode of action. The longer medication list is for treatment-resistant patients. Newly introduced medications or changes in dosage from that in Betrayal are marked with an asterisk. The mechanisms by which I think these medications work will be discussed in my next book, which is now gestating. It will cover how brain neural networks can rapidly reset themselves, sometimes virtually immediately, as is the case in responders to naphazoline eyedrops. This material will be extremely technical, although it is fascinating to me. In the book I also shall describe my personal experience of the good and bad aspects of my practice. Although the good still outweighs the bad, the good is restricted to two items. I can help people who have been ill for many years to feel better or almost normal usually in one to five days. I am stimulated by the challenge of creating new medical paradigms and treatment, an opportunity that is rapidly vanishing for most clinicians in the era of managed health care. The negative aspects of my practice are more numerous and will be described anecdotally. Pointers and pitfalls will be related so that physician burnout may be minimized and interested patients can be informed about what their doctors might be experiencing in a practice dealing with "neurosomatic" disorders such as CFS/FMS, as well as about 100 other related illnesses. The future appears fairly bright and at the present time I am surprised if I am unable to greatly improve a patient's symptoms, although I cannot yet help everyone in five days. It actually takes about three years to explore all treatment options that I use. There are many new medications which extend from being on the verge of release to very early (phase II) clinical trials, which offer promising results by altering different neurochemical pathways than I have previously explored. The possibility of a "cure" using a synthetic neuropeptide to permanently "reset" the brain as one clinical researcher termed it, may have already occurred in one neurosomatic disorder, although longer follow-up is needed. A second group of patients has begun treatment with this possibly curative agent. A subgroup of patients, perhaps 20%, have congenital cervical spinal stenosis and may achieve remission from a decompression laminectomy according to the work of Michael J. Rosner and associates. This group would be particularly vulnerable to "whiplash" injuries as might be suffered in a motor vehicle accident. Such a treatment is rational as I discussed in Betrayal since the upper cervical nerve roots comprise much of the mesencephalic tract of the trigeminal nerve, an important integrator of sensory input. I had not thought that a definitive medical treatment would be found in my lifetime (yes, it was double-blind placebo-controlled, although with a fairly small "n" [number of patients]). A surgical cure had never occurred to me. Antimicrobial therapy is another curative possibility that has been thus far elusive for most patients I see. Transcranial magnetic stimulation, something like Focal electroshock therapy, is another promising technique which works rapidly with few adverse effects if done properly. It is still experimental. My present treatments can also be viewed as resetting one or more neural networks but must be taken regularly to be effective, like insulin for diabetes. Almost all of these medications are quite safe if minimal precautions are taken. If more physicians were aware of these methods, I believe that human suffering from neurosomatic disorders could be markedly reduced. Another technique to dynamically (and immediately ) modulate the synaptic and intrinsic properties of neurons and reconfigure the networks they comprise is by externally altering trigeminal nerve input to the mesencephalic tract. The trigeminal nerve has three divisions (hence the name) which conduct sensory input from the upper, middle, and lower portions of the face. Immediate symptom alteration can be produced by certain kinds of eyedrops for the upper part, nasal dilators and adjustable upper teeth (maxillary) splints for the middle part (see the work of Alexander Chester, Dwight Jennings, and Robert Oliver}, and sometimes lidocaine drops on the floor of the mouth (lower part).

    The vagus nerve is the other cranial nerve which modulates sensory input via the solitary tract in the brainstem. Devices to electrically stimulate the vagus have been implanted subcutaneously in the neck and have been helpful in treatment-resistant epilepsy. Such an approach should be useful in other neroregulatory disorders.

     I have thought for some time that the ultimate treatment for CFS/FMS would be some sort of gene therapy to alter production of proteins that regulated signal-to-noise ratio (e.g. tuning your radio so you hear the music without the static). I did not expect to live to see the technology to accomplish this goal, but I have been noticing that the future keeps getting here faster and faster. In the last five years, drugs like doxycycline have been found to bind to DNA regulatory sequences (operators and promoters) in mammalian cells to turn up or down the activity of a gene. Although most of this work has been done in genetically modified ("transgenic") mice, natural or synthetic substitutes could possibly produce the same effect in humans. It is unlikely that regulating a single gene could significantly alter a polygenic behavior or reconstruct a neural circuit, but this line of research is advancing too rapidly for me to predict the outcome (see Holsboer F. Transgenic mouse models: new tools for psychiatric research [1997] The Neuroscientist 3:328-336).

     I halt sequential trials when the patient is virtually asymptomatic, using other medications if tolerance should develop. These drugs are all relatively free of adverse reactions and do not appreciably interact with one another. A patient taking tacrine requires regular liver function tests. Because of reports of aplastic anemia, felbamate therapy should be monitored with bi-monthly blood counts and liver function tests. The total daily dose of gabapentin may be as high as 5,000 mg. if lower doses are not beneficial. Using this protocol, most patients are dramatically improved in one or two office visits. 


Agents tried sequentially 
Onset of Action 
Duration of action 

1. Naphazoline NCI0.1% gtt+OU 
2. Nitroglycerin 0.04 mg. sublingual 
3. Nimodipine30 mg po 
4.*Gabapentin 100-800 mg.po 
5. Baclofen 10 mg 
6.*Topirarnate 25-50 mg 
7.*Tiagabine 4mg 
8.*Hydergine 2mg 
9.*Tramadol 50-100mg 
10.Oxytocin 5-10 U IM OD 

2-3 seconds 
2-3 minutes 
20-40 minutes 
30 minutes 
30 minutes 
45 minutes 
30 minutes 
30 minutes 
30 minutes 
15 minutes-72 hrs 
3-6 hours

3-6 hours 
4-8 hours 
5-9 hours
8 hours 
12-24 hours 
12-24 hours

8 hours 
4-6 hours 
12-24 hours

**Only the first 10 of 30 medications are posted see Winter issue of The National Forum for next 20.

JAY A. GOLDSTEIN, M.D., 701 N. Glassell St., Orange, CA 92867 


DISCLAIMER; Medicine is an ever-changing science. As new research and clinical experience broaden our knowledge, changes in treatment and drug therapy are required. While many suggestions for drug usage are made herein, this article is intended for educational purposes only and the author, editor, and publisher do not accept liability in the event of negative consequences incurred as a result of information presented in this article. We do not claim that this information is necessarily accurate by the rigid, scientific standard applied for medical proof, and therefore make no warranty, express or implied, with respect to the material herein contained. Therefore the patient is urged to consult his or her own physician prior to following a course of treatment. The physician is urged to check the product information sheet included in the package of each drug he or she plans to administer to be certain the protocol followed is not in conflict with the manufacturer's insert.

When a discrepancy arises between these inserts and information in this article, the physician is encouraged to use his or her best professional judgment.

[Ed. Note: Dr. Goldstein is the author of The Limbic Hypothesis and Betrayal by the Brain, both available from The Haworth Press (1-800-342-9678), numerous medical journal articles, and is in private practice as Director of The CFS Institute.] 

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