1. Napthazoline HCL 0. 1% gtt OU

• If alpha-adrenergic eye drops help a pt feel better, they will also stop his panic attacks (if he has them) The drops are effective in a few seconds and are not addictive, although tolerance may develop. In 1/5 pts there is sign of relief of pain and tender pt sensitivity, as well as decreased fatigue and more mental clarity; also decrease in anxiety level.
• induces cerebral vasoconstriction
• some pts become overstimulated by 0. 1% naph. and complain of nervousness and insomnia. This can be resolved by diluting the product in normal saline until there are no adverse reactions.

Case Report

46 yr old accountant with a history of NIDDM, migraine, had developed asthma and multiple chemical sensitivities at age 42. At age 44, CFS with fatigue, sleep disorder, cognitive dysfunction and fibromyalgia and had to stop working.

• ten seconds after 0. 1% naphazoline eye drops, all her symptoms were gone. She maintained this improvement for the six months she was followed, as long as she took the naphazoline once or twice daily. Her multiple chemical sensitivity resolved as well. 2. Nitoglycerine 0. 04 mg SL - best available market source of nitric oxide; low doses sometimes results in amelioration of symptoms, especially pain, in about 2 minutes. Tolerance often develops.
• NO improves encoding for short-term memory; is anxiolytic; releases dopamine which can relieve fatigue and enhance cognition and attention; inhibits dopamine uptake, and increases the release of serotonin; is a Ca++ channel blocker; stimulates prodn of VIP (important for neuron survival);
• some FMS pts report that NTG significantly potentiates the effect and duration of opioid analgesics - decreased regional NO levels could be related to the IL-2 beta decreased function which would also produce lower CNS levels of serotonin, dopamine, certain prostaglandins, IL-6, and CRH. -NO is involved in the maintenance of spontaneous sleep; many effects of NMDA receptor activation appear to be mediated by NO.
• studies have shown red blood cell shape with altered shapes that are less deformable than normal. NO, at the proper concentration, preserves or enhances red blood cell deformability.
• CFS monocytes do not behave normally; they do not, for example, ingest endometrial cells that have refluxed from the fallopian tubes during menstration, thus leading to endometriosis. The cytotoxicity of macrophages in the peritoneum is related to macrophage ability to produce NO.

Case Report

39 yr old data processor on Effexor and lithium for mood disorder, developed CFS despite her psychotropic meds. She did not respond to0. 04mg of NTG but as dosage was slowly increased had less pain, more energy, more "flexibility", and more cognitive clarity. At 0. 4mg she was symptom free. She continued to feel normal with a NTG patch supplying0. 6mg/hour. At three months follow-up, the NTG was not working as well, but was still very effective.

2. Nimodipine 30 mg - 60 mg tid

• is the most useful agent in Rx of treatment-resistant panic disorder, a related limbic disorder.
• about 40% of pts experience relaxation, increased energy, decrease in tender point sensitivity, improved exercise tolerance, and enhanced mental clarity.
• Ca++ channel blockers are reported to be useful in panic disorder and in potentiating opioid analgesics. Nimodepine is also being investigated in Rx of HIV
• associated cognitivemotor complex. Some CFS pts with developmental learning disorders have a remarkable improvement with nimodepine. It also has anti-depressant effects. (Can order tabs at 1/6 the price from Zurich)
• in almost all responders , nimodepine causes further vasoconstriction of post-treatment SPECT scans. Nimodepine has been shown to release dopamine, serotonin, and acetylcholine. Of these, only serotonin is vasoconstrictive at physiological doses. Tolerance does not develop to the vasodilatory effects of nimodepine, but sometimes does to its amelioration of CFS/FM symptoms. ACE inhibitors such as Capoten are effective antidepressants, which have some limited ability in ameliorating CFS/FM symptoms, probably because they inhibit the breakdown of certain peptides, including the enkephalins. They also stimulates release of NO from endothelial cells.

Case Report

53 year old executive developed CFS six years ago following a very stressful lawsuit. He was not working and estimated his level of functionat 25 - 30 % of normal. He had difficulty reading and retaining information. 30 minutes after taking nimodipine 30mg, he stated he felt"90 % better". He could read , comprehend and retain information. He returned to work and stated he felt like he did "seven years ago".

3. Gabapentin 100 - 300 mg tid

• safe; excreted unchanged; commonest side effects are somnolescence, dizziness, fatigue
• many pts report marked increase in energy after the first dose.
• a remarkably effective anxiolytic in certain pts.
• has antidepressant effects in a few pts, and may have a beneficial effect on the entire spectrum of neurosomatic disorders.
• indirectly increases release of GABA

Case Report

48 yr old CFIDS with nausea, severe fatigue, intermittent diplopia, paresthesias, diarrhea, short term memory problems. - prompt response to nitroglycerine, nimodipine, and hydralazine but developed tolerance to all of them. 100 mg gabapentin made him feel "jet-propelled", dose reduced to 50 mg twice a day . Higher doses make him feel agitated. Continues gabapentin and has returned to pre-illness level of function.

Case Report

53 yr old neuropsychologist with fatigue and cognitive dysfunction for 21/2 yrs, history of irritable bowel syndrome & episodic depression.

no response to naphazoline, NTG, or nimodipine. After taking 300 mg gabapentin she became more energetic, her mood brightened, she could read a neurology article and discuss it afterwards, She continues on 300mg bid - tid and has returned to work. She may try oxytocin in addition because of decreased libido, and mild occipital burning dysesthesia.

4. Oxytocin 5 - 10 u IM od or bid

• Oxytocin has a wide range of behavioral effects besides its classical peripheral endocrine actions i. e. milk ejection during suckling; stimulation of uterine contractions during labour; expediating delivery of the placenta.
• Oxytocin is often co-localized with CRH; it is worthy of a trial in treatment resistant cases of CFS and related neurosomatic disorders.
• oxytocin neurons project to many areas of the limbic system and brain stem, as well as to the frontal cortex. Brain oxytocin is involved in the organization of maternal behavior, sexual behavior(male & female), feeding, social behavior, and memory. It also has effects on CVS, autonomic, and thermoregulatory processes. It has been found to inhibit tolerance to morphine and cocaine. Other agents with this property, such as nimodipine and NTG, are effective in treating CFS. Cholecystokinin antagonists, which also have this property, somatostatin or octreotide may be useful in CFS therapy.
• oxytocin modulates hippocampal function and is an arterial vasoconstrictor. - appoximately one-fifth of patients have a good response to oxytocin after failing to respond to numerous other agents. Cognitive clarity is the most responsive symptom, with fibromyalgia pain second. Energy is not increased in many responders. Some pts do well on 5 units, but become agitated and have some return of symptoms on 10 units.
• systemic administration of oxytocin does not penetrate the blood-brain barrier; as little as 0. 003% reaches the brain. It has a plasma half-life of 1-6 minutes. Thus it must either be an extraordinary placebo, or it must exert its central effects through peripheral nerves. 90% of the vagus nerve fibres are afferent (from gut to brain). This explains the role of central oxytocin in regulating gastrointestinal function and how vagal afferents transfer information from the gut to the brain, a key concept in understanding CNS regulation by peripheral nerves, as well as the food intolerance commonly encountered by pts with neurosomatic disorders. Efferent vagal nerves regulate the activity of the gut neuro- endocrine system. Oxytocin reaches the vagal motor nucleus and releases gut hormones which can be measured in the blood stream. Ingested food causes activation of the "satiety hormone" cholecystokinin which binds to vagal receptors and activates afferents to inform the brain about how much food is entering the gut and whether food-seeking behavior should continue. Both food intake and cholecystokinin cause sedation, which may be oxytocin mediated. Intraperitoneal injection of cholecystokinin induces maternal behavior, therefore afferent vagal mechanisms not only influence gastrointestinal motility and secretion, they also influence behavior and endocrine patterns. It follows that food intolerance could result from dysregulated gating of affterent sensory input to the brain. Case Report- oxytocin produced a manic episode in a 58 yr old mildly demented physician with CFS who was taking Zoloft 100 mg daily. Reducing the Zoloft dosage prevented further mania, and the combination markedly alleviated his symptoms, including the dementia. Case Report- a 56 yr old physician with CFS and treatment resistant depression was refused ECT therapy because of cognitive dysfunction. He resolved all his symptoms 15 minutes after receiving 10 u of oxytocin IM, but became quite flushed and hypertensive requiring IV nifedipine. On subsequent lower dose of oxytocin his BP was fine. BP must be monitored after oxytocin administration. The effectiveness of oxytocin in certain pts reinforces the pluripotential nature of virtually all transmitter substances; patient response depends on which cells are affected, not the nature of the transmitter itself.

Case Report

66 yr old highly specialized auto mechanic had been well until 4 years before when he developed episodes of profound fatigue associated with anterograde and retrograde amnesia. He forgot how to repair cars and could not work. He was amnesic for large periods of his life. Neurological consultations yielded the diagnosis of variant global amnesia and the episodes were finally halted by Dilantin, but his memories were not restored. Brain MRI was normal. SPECT showed frontotemporal hypoperfusion bilaterally. EEG was normal. At the time of consultation he was profoundly fatigued , felt his life was ruined and was consider-ing suicide. 20 minutes after receiving 10 units of oxytocin I. M. , he had regained much of his energy. The next morning he remembered how to repair automobiles, as well as many past events, ( perhaps indicating a need for protein synthesis for synaptic remodeling of neural circuitry and the need for sleep to self-reactivate the neuronal circuits of long-term memory. As he continues oxytocin, he continues to regain memory. Pindolol also has enhanced memory reacquisition, but caused hypomania in this patient. His dorsolateral prefrontal cortex lesions maycause glutamatergic hypofunction and may be attenuated by glycine, as are negative symptoms in schizophrenia.

Case Report

Pseudoseizures respond to oxytocin also. A 38 yr old medical secretary developed CFS/FM symptoms after receiving a silicone breast implant. She also developed dystonic movements, stuttering and lapses of consciousness. Neurological workup was normal except for bilateral frontotemporoparietal and posterior cingulate hypoperfusion on SPECT. Trials of xanax, ativan, nortryptyline, dilantin, and benztropine were notbeneficial. She had no response to naphazoline or NTG. Nimodepine mildly improved all her symptoms. One hour after receiving 10 units of oxytocin she was alert, had no fatigue, no pain, and no further posturingor grimacing . A minimal speech dysfluency remained which responded well to gabapentin. Many, if not all pts with pseudoseizures have a comorbid diagnosis of panic disorder.

Pseudoseizures are common and are seen in pts who have models for seizures (often epileptics themselves), who have had a childhood loss, or who have been diagnosed with personality or somatoform disorders. Secondary gain is not a prominent feature, and the diagnosis should be suspected in the presence of the above features plus absence of self-injury, incontinence, or an elevated post-ictal prolactin level. Patients with pseudoseizures respond well to a neurosomatic treatment protocol.

5. Pyridostigmine 30 - 60 mg po

• Some medications e. g. naphazoline eye drops andpyridostigmine have a peripheral mode of action, but can produce dramatic effects on centrally-mediated symptoms and cerebral perfusion. Pyridostigmine is a peripherally acting cholinesterase inhibitor. Tacrine is a centrally acting cholinesterase inhibitor. Tacrine is sometimes effective where Mestinon is not, and vice-versa.

6. Hydralazine 10 - 25 mg po

• responders report amelioration of one or more target symptoms within an hour after a dose of 10 to 25 mg.

Case Report

44 yr old flight attendant developed CFS after Rx for an acute diarrheal illness. Consultation occured after 2 years of not being able to work. Sxincluded cognitive dysfunction, non-restorative sleep, severe fatigue, dysequilibrium, blurred vision, benign fasciculations in his legs, myalgia, arthralgia and night sweats. Trials of i) naphazoline eyedrops. ii) NTG, iii)nimodepine, iv) Mestinon, v) and mexilitine were of no effect. 30 minutes after taking vii) hydralazine he felt much better. This improvement continued for the next 18 months. He still had some symptoms, namely diarrhea and bloating. He received trials of vii) felbamate, viii) Risperdal, ix) gabapentin, x) baclofen and xi) oxytocin, without effect. xii) Tacrine 10 mg helped him feel more relaxed. He has returned to work and continues on hydralazine 25mg tid.

7. Baclofen 10 - 20 mg tid

• one of the most effective treatments for neurosomatic disorders, an oral GABAB agonist, especially successful in treating central pain. This central pain may manifest itself as fibromyalgia, headache, low back pain, or other regional pain syndromes. It is often useful as an anxiolytic, and sometimes increases alertness. (tolerance to this latter effect is quick to develop. ) Occasionally can make a pt feel worse, perhaps by reducing CRH secretion or by inhibiting hippocampal function.

Case Report

48 yr old post-nephrectomy developed CFS. No response to anxiolytics or antidepressants; c/o persistant low back pain, neg MRI, no response to epidural steroid injections. Like many CFS pts, multiple medications were required to treat him. Gabapentin helped him feel more relaxed, mexilitine eliminated his testalgia, and baclofen greatly reduced his diffuse pain as well as his lower back pain, which was then completely relieved with lidocaine trigger point injections into the lumbosacral triangles.

Case Report

58 yr old Rx’d in hospital for pericarditis with prednisone subsequently developed sepsis-----after discharge developed severe fatigue, cognitive dysfunction, and diffuse pain, and severe low back pain. He had some improvement with Zoloft and gabapentin but after a month of treatment still did not feel well enough to return to work. He suffered panic attacks despite his treatment regime. Thirty minutes after receiving baclofen 10 mg he reported that his back pain and anxiety were completely gone, and that he felt much more alert and energetic. This improvement has persisted for several months.

9. Mexiletine 150 mg po

• has few serious adverse effects in low dose. It has been successfully used for neuropathic pain, especially dysesthesias. It may act by increasing central CRH secretion. It may exert its effect on neuropathic pain at the dorsal root.

10. Tacrine (Cognex) 10 mg

• approved for Rx of Alzheimer’s dementia, it is a centrally- acting cholinesterase inhibitor, increasing brain levels of acetylcholine. It works differently in CFS than the peripherally acting cholinesterase inhibitor, pyridostigmine (Mestinon). Tacrine is sometimes effective when Mestinon is not, and vice-versa. Those who take Tacrine require bi-weekly monitoring of liver function tests. Tacrine blocks voltage- gated K+, Na++, and Ca++ channels. Other agents useful in CFS also block K+ channels ( gamma globulin, dihydropyridine, Ca++ channel blockers, 5-HT2 agonists, sulfonylureas, and the antiarrhythmic sotalol. ) Tacrine also seems to block NMDA channels in the open state, prolonging NMDA response. K+ channel blockers should be useful in neurosomatic disorders because they produce membrane depolariza- tion and release of neurotransmitters.

Case Report

33 yr old developed CFS after treatment for amoebic dysentery and giardiasis and had to drop out of her Ph. D. program. She had a history of endometriosis and interstitial cystitis. She did not benefit from multiple antidepressants, IV ascorbic acid, antifungals, or kutapressin. She complained of multiple chemical sensitivities and a disorder of initiating and maintaining sleep, for which she took Serax. She was tender over 18/18 fibromyalgia tender points. She had moderate responses to naphazoline, nitroglycerine and nimodepine, which increased her energy somewhat. Gabapentin 100 mg made her "much more alert" but she stated she felt too "speedy". The next day she took 100 mg of gabapentin then hydralazine 25 mg, which eliminated her tender points. She estimated her energy level at 40% compared to 10% (she could barely walk when she came in. ) After tacrine 10 mg she stated that she felt much better, and after 10 mg more reported that she felt the best she had in five years. She stated that tacrine, the most beneficial medication she tried, made her more alert, increased her energy, enhanced her "cognitive processing and assimilation of information", and gave her a general feeling of well-being. She continues on this regime (tacrine 20 mg tid, gabapentin 100mg tid, and hydralazine 25mg bid - tid ) and is returning to graduate school.

11. Risperdal 0. 25 - 0. 5 mg bid to tid

• is a high-affinity 5-HT2 antagonist and a low-affinity dopamine (D2) antagonist. At the low doses used for CFS, the D2 antagonist effect, useful in schizophrenia, is not very prominent. (The antidepressant Serzone is a 5-HT2 receptor antagonist as well as a serotonin reuptake inhibitor. ) The 5-HT2 receptor is implicated in neurosomatic disorders because: A) it is located in the cortex, caudate, limbic system, midbrain, and hypothalamus. B) It influences vasoconstriction, migraine, anxiety, depression, and sleep, all functions relevant to CFS. The 5-HT1c receptor is closely related to the 5-HT2 receptor, and is also involved in appetite, learning and aversion. Risperdol blocks frontal cortex 5-HT2 sites & increases stage 3 and 4 slow wave sleep . Drug effects usually occur in 30-45 minutes but peak plasma levels are not reached for two hours. C) The 5-HT2 receptor is also involved in upregulating limbic (especially hippocampal) glucocorticoid receptor density. There is reason to believe that hippocampal glucocorticoid and possibly mineralocorticoid receptor density is increased in CFS, especially since CFS patients have decreased CRH secretion. Hippocampal corticosteroid receptors are involved in the inhibitory feedback mechanism of glucocorticoids on adrenocortical activity. Antidepressants upregulate these receptors. Recent evidence indicates that the density of these receptors can be affected for a lifetime by genetic predisposition interacting with early childhood experiences, thus altering the stress response later in life and possibly deranging other limbic functions. 5-HT2 antagonists decrease limbic glucocorticoid receptor density and should have a beneficial effect in this scenario.
• Mineralocorticoid receptors are involved in the sensitivity of the stress response system: this concerns processes related to the evaluation of situations and the corresponding response selection. Glucocorticoid receptors are involved in the termination of the stress response, and in processes concerning the consolidation of information i. e. , learning and memory. Behavioral plasticity is determined by the balance of mineral- ocorticoid and glucocorticoid receptors. Administration of a mineralocorticoid receptor antagonist (Aldactone) along with Risperdal, should have a beneficial effect since it may attenuate serotonin responses if there is an imbalance between mineralocorticoid and glucocorticoid receptor -mediated effects. Aldactone has been used for years to treat PMS. The symptoms of CFS are quite similar to PMS, and women with CFS usually report a premenstual exacerbation of their symptoms. Aldactone only helps occasionally, but the effect is rapid (30 minutes). Risperdal plusEffexor often work well in combination.

12. Pindolol 5 mg bid

• is a beta-blocker which is also a 5-HT1A antagonist. SSRI’s do not increase serotonin levels in the projection areas of the raphe nuclei after a single dose. This lack of effect is thought to be due to stimulation of a 5-HT1A presynaptic autoreceptor that follows reuptake blockade. Thus it appears that blocking the 5-HT1A autoreceptor could augment the antidepressant effects of SSRI’s by enabling serotonergic nerve terminals to release more serotonin. Pindolol has this effect. Pindolol is not a pure 5-HT1A antagonist , but is actually a partial agonist. It blocks 5-HT induced prolactin secretion, but by an agonist mechanism increases basal cortisol secretion. There is also co-operactivity with the 5-HT1A receptor and the 5-HT1c receptor which is antagonized by risperdal. Pts who respond to pindolol do so within 30 minutes. It takes longer when pindolol is used to augment MAOI’s or SSRI’s. Pindolol markedly reduces the latency period of onset of Paxil ( usually to one week). Thus pindolol can benefit neurosomatic pts by increasing glutamate-stimulated norepinephrine release, and also serotonin release in association with antidepressants.

Case Report

57 yr old clinical psychologist with a history of recurrent depression and migraine, diffuse musculoskeletal pain, and cognitive dysfunction interfering with her work. She was tender over 18/18 of the characteristic fibromyalgia tender points. She had no response to naphazoline or nitroglycerine, but 30 minutes after taking nimodepine she was symptom free, and remained so for two months when she developed a cold and relapsed. All symptoms were relieved by Mestinon and gabapentin and she did well for the next 4 months. Then she developed bronchitis and multiple root canal surgeries and relapsed again. She developed a 3" area of burning dysthesia over her left elbow, as well as her typical CFS symptoms. These were promptly relieved (20-30 minutes) by 5 mg of pindolol, which she now takes three times a day. She can tell when it is time to take another pindolol because her elbow starts to burn again.

13. Lamotrigine 25 - 50 mg od

14. Sumatriptan (Imitrex) 3 - 6 mg SQ- or 25 mg po

• It is now believed that migraine headaches are caused by dysfunctional neural transmission through the trigemino- vascular system and not by changes in brain vessel diameter. A "neurogenic inflammatory response" is postulated which causes release of numerous peptide mediators which could be responsible for the pain, nausea, photophobia, auras, and phonophobia of the migraine attack. Headaches may represent a pain modulation disorder such as is seen in fibromyalgia syndrome. Imitrex, an agonist of the 5-HT1D receptor is postulated to prevent the release of the peptides, thus stopping the chain of excitation. It may act at the level of the meninges since it penetrates the blood-brain barrier poorly. Imitrex may also block trigeminal nerve transmission directly, which would explain its rapidity of effect in pts who respond in 2 -3 minutes. Lidocaine also blocks neurogenic plasma extravasation in the dura matter with a time course similar to Imitrex, perhaps explaining why mexiletine, a lidocaine analog is often effective in reducing the headaches of some neurosomatic pts, as is lidocaine itself.
• Imitrex and ergot amines decrease headache of many sorts, including cluster, classic and common migraine, tension-type headache of drug withdrawal, as well as headache caused by meningo- vascular irritations such as meningitis and subarachnoid hemorrage. SQ Imitrex works rapidly, aborting 74% of migraine headaches within 15 min Side effects such as chest pain (thought to be esophageal in origin), vertigo, fatigue, worsening of headache, nausea, numbness and a feeling of dysphoria or "strangeness" can be eliminated with the non- selective serotonin receptor antagonist Periactin 4 mg po. Serious adverse events can occur when sumatriptan is given to pts with undetected subarachnoid hemmorage, significant CAD, or to those on MAOI’s. When given to pts with neurosomatic disorders, Imitrex increases growth hormone. Many pts with fibromyalgia have decreased levels of growth hormone. In most patients only pain is decreased. A minority of pts report improvement in all neurosomatic symptoms.

Case Report

46 yr old minister with diffuse parasthesias, myalgia and arthralgia, intermittent fatigue, headaches, panic attacks, cognitive dysfunction, and numbness in both arms and legs since 1988. All symptoms were made worse by stress. He had been seen by neurologists, rheumatologists, and immunologists. He had fibromyalgic tender points. He had intermittent chest pain and parasthesias in his right great toe and left heel pain. He had sleep dysfunction and had developed a facial tic. Over the years his dysthesias became more painful. He had intermittent blurred vision and was often unable to recall what he had said 2’ before. He denied depression. He had nocturnal panic attacks and significant exertional intolerance. His tics were partially controlled , first with calcium channel blockers and then with Periactin. He did not respond to i) SSRI’s, ii) tricyclic anti- depressants, iii) Xanax, iv) hydralazine, v) nimodepine, vi) Mestinon, vii) clonidine, viii) captopril, ix) baclofen, x) mexiletine, xi) felbamate, or xii) nicotine patches. He had an exellent response to xiii) nitroglycerine but developed tolerance after 2 months. Brain MRI was normal. He complained of severe fatigue. Sometimes his feet became completely numb. xiv) risperdal did not help him, xv) naltrexone (Trexan) decreased his tic but made him feel "spacey". He also tried xvi) tacrine, xvii) gabapentin, xviii) hydrochlorathiazide, xix) ergot, xx) pindolol, and xxi) aldactone. xxii) IM oxytocin made him worse. He was given xxiii) Imitrex, which resolved all his symptoms except for the tic. He could not afford Imitrex and was enrolled in a marketing study which enabled him to receive it free. His symptomatic improvement has been maintained on twice-daily injections of Imitrex.

15. Zantac 150 mg bid

• an H2 receptor blocker, is often successful in alleviating the symptoms of acute mononucleosis. It must act peripherally since it penetrates the blood-brain barrier poorly. Tagamet can cause restless leg syndrome and tardive dyskinesia, suggesting deficiency of GABA opioids and dopamine, since agonists of these agents are used to treat restless leg syndrome. The H2 blocker famodipine had beneficial effects on the negative symptoms of schizophrenia in an open study. Histaminergic neurons, located in the posterior hypothalamus, suppress interleukin-1 beta. IL-1 beta antagonism may be involved in the pathophysiology of CFS. H2 blockade could attenuate this IL-1 beta suppression. Increased central IL-1 beta may produce immunosuppression by increasing CRH, thereby decreasing cytokine excess of acute mononucleosis. Central IL-1 beta also stimulates central histamine release, a process involved in elevating body temperature. When a CFS pt responds to Zantac the onset of action is similar to that seen in acute mono, i. e. , one or two days at a dose of 150 mg bid. Usually all the symptoms are ameliorated. Some pts cannot tolerate Zantac because it makes them "hyper". Inhibiting GABA certainly could cause stimulation, especially if the pt has a hx of panic disorder. Histamine may also induce melatonin secretion by stimulat- ing pineal cyclic AMP. Histamine may thus be involved in sleep-wake cycles and other aspects of circadian physiology. Case Report-50 yr old probation officer post-op developed typical CFS/FMS symptoms She was started on Zantac 150 mg bid and felt much better after two days in all respects. Over the next three years she was prescribed Zoloft for depression and did well until she developed " brain fog", which was greatly helped by the addition of gabapentin. She was referred to a gastroenterologist by another M. D. for evaluation of her heartburn. Her Zantac was discontinued and she was given Losec with assurances that it would "work better" than Zantac for her CFS as well as for her reflux esophagitis. Three days after stopping Zantac she began sleeping 14 hours a day and experienced severe malaise. After several days of this relapse, she restarted her Zantac and resumed good health in 48 hours.

16. Sinequan elixer 2 - 20 mg hs

17. Zoloft 25 - 50 mg qAM or Paxil 10 - 20 mg qAM

18. Bupropion (Wellbutrin) 100 mg tid

19. Nefazodone 100 - 300 mg bid

20. Effexor 37. 5 - 75 mg bid

• marketed as especially useful in treatment-resistant depression, its adverse reaction profile is similar to the SSRI’s, except that it can raise BP in some pts and more frequently causes nausea. Try SSRI’s and Wellbutrin before considering Effexor. The drug blocks serotonin, norepinephrine, and dopamine reuptake and typically takes two or more weeks to respond to, It is sometimes helpful to use Risperdal and Effexor together. Start dose at 18. 5 mg with food. It may be helpful to drink ginger ale with it , since ginger reduces nausea.

21. Glycine powder 0. 4 Gm/kg/day in juice or Cycloserine 15 - 50 mg od

• (available otc in USA- read potential risks and precautions before prescribing-J. S.)Significantly reduces the negative symptoms in schizophrenia.

Case Report

53 yr old real estate developer post-op coronary angioplasty developed weakness and fatigue, a positive Tensilon test, and an EMG consistant with a neuropathic process, CPK was elevated. Three years later after a MVA without head injury he developed cognitive dysfunction and a severe daily headache. SPECT scan showed frontotemporal hypoper- fusion. Muscle biopsy was consistant with denervation. It was concluded that he had an autoimmune polyneuropathy. None of a panoply of medications produced dramatic improvement. High doses of oral glycine were started. There was no change in his status until he reached 15 gm per day, at which time his headache decreased somewhat. At 20 gm per day, he had a moderate improvement in energy and was able to take walks and go bicycle riding for the first time in seven years. He stopped taking Mestinon which had helped his weakness somewhat. His headache disappeared and he was able to organize and complete paperwork. He is currently titrating his glycine dosage to optimum levels. He weighs 80 kg. He has almost complete relief of his symptoms at a dose of 0. 4gm/Kg/day. Increasing glycine to 40 gm/day did not confer any additional benefit and gave him a headache.

Glycine crosses the blood-brain barrier poorly and undergoes peripheral metabolism. For this reason it must be taken in very high doses. Glycine powder mixed with juice is palatable. Glycine has had no serious adverse effects so far in any of my patients. Cycloserine (Seromycin) appears to be a significant improvement over glycine in the treatment -resistant patient.

22. Talwin

• inhibits NMDA-stimulated norepinephrine release as a sigma receptor agonist. Sigma receptors play a role in motor function and in the motor effects of the antipsychotic drugs. Talwin may act as an NMDA co-agonist (like glycine) in the neurosomatic patient. Only the occasional extremely treatment-resistant individual has felt much better after taking Talwin-Nx.

Case Report

30 yr old lady with a ten year history if serious depression, severe fatigue, cognitive dysfunction, marked insomnia, and fibromyalgia. She had failed treatment with every standard psychotropic agent , alone and in combination, and had not responded to multiple courses of ECT. She had severe panic disorder and was taking 10 mg of Xanax a day as well as 100 mg of Zoloft at the time of consultation. She did not respond to most of the above medications but felt "10%" better on baclofen and gabapentin. Surgical cingulotomy was being considered because of severe suicidal ideation. While she was waiting for the neurosurgical consultation, she was given one tablet of Talwin-Nx. She rapidly felt better, less depressed, much less anxious, had less pain and more energy. Since it made her feel somewhat "goofy" the dose was decreased to 1/4 tablet. She could sleep much better taking Talwin hs. The effect of Talwin was enhanced by high-dose glycine. Capoten further improved her depression.

She is now working part-time in a boutique and has a boyfriend. Case Report-59 yr old political worker became extremely ill within hours of receiving a flu shot. She developed severe exhaustion, diffuse pain, and significant cognitive dysfunction. She had a history of medication intolerance, and recurrent bouts of depression. She had not responded to any psychotropic medication before and did not respond to the first twenty medications above. She improved slightly with naphazoline which eliminated a headache. All her symptoms abated with one Talwin-Nx. She is now doing well on one Talwin-Nx tablet 5 times daily.

23. Diamox

• Patients with neurosomatic disorders will occasionally have a reduction in symptoms with Diamox. It is a carbonic anhydrase inhibitor and is used primarily to reduce intraocular pressure in glaucoma, and to treat high altitude sickness. It has recently been recommended as a possible treatment for bipolar disorders. The commonest side effect is parasthesias. Carbonic anhydrase is located in many neurons and glia. Neurons that are excited by CO2 are common in the nervous system. Most are suppressed by increased levels of CO2.

Case Report

41 year old graphic artist developed post-traumatic fibromyalgia after a MVA. She suffered for six years with diffuse pain, fatigue, cognitive dysfunction, exercise intolerance, sleep disorder, blurred vision, parasthesiae, dysequilibrium, dysarthria, photophobia, decreased libido, irritable bowel syndrome, night sweats, PMS, chest pain, cold hands and feet, and heat and cold intolerance. She had marked improvement with naphazoline eye drops. After taking nimodepine and hydralazine, she was able to walk up and down the stairs of the office buiding several times. Ultimately she developed headaches from these medications and they were discontinued. Naphazoline was still helping but tolerance was developing. Diamox 250 mg eliminated her pain, helped her to feel relaxed, and markedly reduced her other symptoms. Occasional re-emergence of pain is managed nicely by prn baclofen.

24. Vitamin C

• may be beneficial to some pts with CFS. There are high concentrations of vit C in the brain. Oral vIt C Rx has been disappointing IV Vitamin C modulates the effects of glutamate and dopamine. Ascorbate has been found to be neuroprotective of free radical damage especially by inhibiting a redox site on the NMDA receptor. Ascorbate, therefore, may be considered to be an NMDA antagonist. Ascorbic acid with EDTA has been shown to be an effective treatment for depression. Administration of ascorbic acid is done in doses of 25 - 50 grams diluted in half-normal saline or Ringer’s lactate over about 90 minutes. It is beneficial to add 500 mg of calcium gluconate ( since ascorbic acid is a calcium chelator and could possibly lower serum calcium). Adding 1 gram of magnesium sulfate is also recommended because ascorbic acid can cause Mg++ shifts from extracellular to intracellular compartments. Responders to IV ascorbic acid generally feel better in most respects the day after treatment. Since ascorbic acid is not tolerated well in patients with glucose-6-phosphate dehydrogenase deficiency, measuring levels of this enzyme with a blood test before initiating IV therapy is recommended. There is data that ascorbic acid may reduce the toxic effects of alcohol. Peptide amidation is an ascorbate-requiring process that synthesizes active hormones from inactive precursors. Several neuropeptides may by hyposecreted in CFS and FMS. Ascorbate is an essential cofactor for the enzyme which metabolizes dopamine to norepinephrine. It is required for release of acetylcholine and norepinephrine from synaptic vesicles. Ascorbate enhances survival of cultured brain neurons and has an immuno-modulatory effect in HTLV-1 asssociated myelopathy. It enhances NK cell function, often quite low in CFS. It would be in the best interest of patients who have not responded well to other agents to be offered this treatment.

25. Hydergine

• is sometimes effective in neurosomatic disorders in a dose of about 9 mg per day, and it may be useful in Parkinson’s disease in a dose of 15 - 30 mg per day. Hydergine alters dopaminergic and cholinergic transmission. It has a profile of a selective D2 agonist, and can augment hippocampal cholinergic function while decreasing striatal cholinergic function, perhaps increasing energy and memory, while decreasing Parkonsonian symptomatology

Case Report

42 yr old landscape architect with a 20 year history of CFS, not working for the past 6 years. Symptoms included non-restorative sleep, fatigue, bruxism, cognitive dysfunction, arthralgias, and feeling tense. Trials of antidepressants had not helped. He complained of dyspnea on exertion, a common symptom in neurosomatic patients. He did not respond to Sinequan which made him quite groggy. No response to naphazoline or nitroglycerine. He felt much more alert after nimodepine but it did not alter his diffuse pain. However, after taking hydralazine 25 mg he stated he could read a book and retain the basic facts, which he had not been able to do for years, and he had much less pain. At one week follow-up. he stated " I haven’t felt this good in years. " He was able to discontinue NSAIDs and could be physically active in his work.

At six months follow-up, he was still feeling fairly well, but had some weakness in his arms, a new symptom. He still had dyspnea on exertion, air hunger frequent headaches, and some arthralgia. He was still taking nimodepine qid as well as hydralazine, . He had no response to the addition of mexiletine or Mestinon, but after 2 mg of Hydergine he felt more alert. The Hydergine worked so well for him that over the next year he was able to discontinue the other medications. One and a half years later he allowed himself to run out of hydergine and suffered a severe relapse. He resumed nimodipine, ASA , and hydralazine with no effect. One-half hour after taking 2 mg of hydergine he stated " I feel fine. " He continues on hydergine 1 mg tid. If he forgets to take it he develops restless legs and fatigue and cannot sleep.

26. Felbamate (Felbatol)

• 400 mg tid- is an antagonist at the glycine co-agonist site ofthe NMDA receptor. It also potentiates hippocampal GABA receptor chloride currents. GABA agonists may be useful in treating central pain conditions, including FMS. Felbamate and gabapentin may synergize in the neurosomatic patient. Felbamate can cause aplastic anemia (2 deaths worldwide so far-Sept ‘95 ) ( No deaths since routine haematologicmonitoring)

27. I. V. lidocaine 200 to 300 mg in 500 ml half normal saline

• is a rapidly effective analgesic in FMS pts. The effect sometimes last for days or weeks, andoften global symptoms respond. About 50% of patients refractory to alloral agents respond to this. I. V. lidocaine has the unusual property of greater symptom relief and duration of action with each successive use. plateauing after four infusions, and lasting 3 - 7 days. It is THE most effective agent for neurosomatic disorders.
• lidocaine blocks the reuptake of norepinephrine, GABA, & choline, and lowers substance P. -I. V. lidocaine, useful in neuropathic pain, is also an effective treatment for FMS. When it acts only as an analgesic, cerebral blood flow is increased. When symptoms are globally improved, CBF is decreased as with all other rapidly-acting agents.

Case Report

• 54 yr old with CFS for 3 yrs. complained of exhaustion, diffuse pain, panic attacks, heartburn, sleep disorders, cognitive dysfunction, and headaches. She was often bedridden with fatigue, pain & weakness. All treatment trials had been unsuccessful. She was taking high dosesof Xanax for her panic disorder. Her husband had to carry her into the office. After given lidocaine 200mg in normal saline over 2 hours, she stated, " I feel 100% better. " and did a tap dance in the reception room. Benefits from the infusions persist for 7 - 14 days. It improved many of her symptoms, not just her pain.

28. Pondimin 20 mg

29. Cozaar 50 mg

• often helps as an antidepressant & anxiolytic as well over time

30. Ultram 50 mg (tramadol)

• an analgesic, it binds weakly to the u opioid receptor and blocks reuptake of NE and serotonin.

31. Symmetrel 100 mg

32. Cylert 37. 5 mg

33. Manerix 150 mg

34. Nicotine skin patch 1/2 of a 5mg

• Nicotrol patch in a nonsmoker. Works on nicotinic cholinergic receptors causing release of dopamine and NE.

35. Pergolide or parlodel ( works like Sinemet )

36. Deprenyl 5mg bid

• works as an MAO inhibitor

37. Dexedrine 5 mg ii bid

38. Ritalin 10 to 20 mg

39. Valproic acid 250 mg

• an antiseizure medication, it is good for anxiety and panic disorder. It is GABAergic

40. Midodrine ( Gutron )

• a peripheral alpha-1 agonist, it can increase BP e. g. inneurally-mediated hypotension or orthostatic syncope, and increases energy. Alpha -1 agonists have a neuronal excitatory function by inducing depolarization in the pontine reticular formation, thalamus and spinal cord. Available from Victoria Apotheke Zurich.

41. Modafinil

• a centrally acting alpha-1 agonist; often useful in narcolepsy, not habit forming like Ritalin or dexedrine. Victoria Apotheke Zurich.

42. Vigabatrin

• an antiseizure medication; often works if there is concommittant borderline personality or sometimes even psychosis.

43. IV. gamma globulin 5 gm at a time

• often takes four doses to see a response. I. M. gamma globulin q 1 wk- start with 1cc, then 3cc, then 3cc each buttock; max dose for a large person is 5cc in each buttock. Do IgA level first. If patient has IgA deficiency he will produce antibodies against the antibodies in the gamma globulin. Gamma globulin blocks K+ channels ( as do sotolol and tacrine ) and produce membrane depolarization and release of neurotransmitters.

44. Kutapressin 2 ml I. M. od. Do mini-skin test first; . 10 cc intradermally

• Need two months to see an effect.

45. Biaxin 250 mg

• binds to motilin receptors in the brain; only works occasionally

46. "Dopaminergic cocktail "

• of 1)Hydergine 2mg tid for 3 days, then add 2)Symmetrel 100 - 200 mg tid for 3 days, then add 3) deprenyl 5mg bid for 3 days, then, if necessary add 4) bupropion 100 mg tid (it takes 4 - 6 wks to work) Drug Tolerance-large doses of inositol (inositol poorly penetrates the blood-brain barrier) affects the sensitization of the alpha-1 receptor and can sometimes reverse tolerance to a previously helpful medication.

Case Report

16 yr old, home bound for 2 years with CFS, too cognitively impaired toreceive home tutoring. She initially had excellent response to Zantac, naphazoline, nimodepine, oxytocin, and several antidepressants, but thebenefit was always short-lived. After taking one gram of inositol she felt considerably better and was encouraged to resume agents to which shehad developed tolerance. As long as she continued to take inositol 1 gmqid, these medications were again effective. She has returned to high school and will be graduating shortly.