I was reading the Topamax posts and remembered that I saw where Dr. goldstein had it on his list of meds that are considered for these chronic illnesses.
If this has been posted before, feel free to delete it. Or maybe someone will pick up on something they've forgotten about.....
I got a real kick out of his Viagra comments....
Tiptoe Through The Treatments
A Brief Guide To Some of What's New Since
"Betrayal of The Brain"
By Jay A. Goldstein, M.D.
************************************
Acetyl-L-Carnitine Adderall Amantadine Ambien Aricept Baclofen Vitamin B12 BuSpar Clonidine Dexedrine Depakote Dilantin DHEA Felbatrol Gabitril Gingko Biloba Ginseng Saponins Gotu Kola Honey Bee Venom Hydergine Kava-Kava Ketamine Klonopin Kutapressin Lamictal IV lidocaine Marinol Methadone Nicotine Patch or Gum Papaverine SA St. John's Wort (Hypericum) Tasmar (Tolcapone) Topamax Viagra Zyprexa
**************************************
Acetyl-L-Carnitine: In theory, a good drug. It should work as an acetyl group donor to increase acetylcholine, and the camitine has already been shown to be effective in a double-blind experiment by the Drs. Plioplys. Acetyl-L-camitine also increases the levels of nerve growth factor (which are four times normal in the spinal fluid of FMS patients) and increases other transmitters like adenosine and ATP. In practice, a semi-dud.
Adderall: An amphetamine combination that a few patients find more energizing than plain dexedrine. Only about a third of CFS patients have a good response to stimulants, which act by squeezing doparnine (DA) and norepiniphrine (NE) out of neurons and glia. If these transmitters are much too low already, giving stimulants will ftirther lower the signal-to-noise ratio (STN) and increase symptoms.
Amantadine: A weak NMDA antagonist. HelpfW for a few patients. Doses higher than the PDR recommends may be more effective, but there is an increased risk of adverse drug reactions (ADRs) when exceeding this dose. Israelis have given 100 mg IV with good results in neurogenic pain. IV amantadine is not available in the USA. Amantadine, ketamine, dextromethorphan, and a new MNDA antagonist, memantine, can be used in trigger point injections as well as gel applications for local pain.
Ambien: The best sleeping pill. Does not cause dependence except in unusual circumstances.
Aricept: A cholinesterase inhibitor marketed for Alzheimer's disease. Has the advantage of once-a-day dosing and no requirement for liver function test (LFT). Does not work as well as Cognex, perhaps because it is not a potassium channel blocker. Cognex has several effects on neurotransmitters relevant to CFS/FMS.
Baclofen: A greatly under used medication. A GABA-B agonist with few ADRs, it has an immediate onset of action and is still in my top 10.
Vitamin B12: Besides being vital to transmethylation (which helps to synthesize NE), B12 2mg. orally in AM decreases inappropriate daytime melatonin secretion, thereby aiding in the treatment of the delayed sleep-wake cycle many CFS patients experience. Very large doses (10 mg) may aid transmethylation.
BuSpar: The ideal anxiolytic in all respects except efficacy. Best used as an SSRI augmentation agent, especially combined with Visen (not generic Pindolol). Augmentation strategies, of which there are many, do not work nearly as well in CFS as they do in major depression disorder.
Clonidine: Another greatly underused drug. Can be good for central pain, ADD, anxiety. Helps all symptoms in some patients. Eliminates nightmares. Safe and cheap. Comes in a patch that lasts all day. Better than Zanaflex, another alpha-2 agonist. Tolerance and depression have not been much of a problem. ADRs to clonidine can be reversed by yohimbine, an alpha-2 antagonist. Guanfacine (Tenex) is a less sedating alpha-2 antagonist with a 24-hour duration of action.
Dexedrine: An effective stimulant. Makes some patients calm also. May synergize with Ultram. Desoxyn may be better but has neurotoxicity. Many patients like Adderall more.
Depakote: In the CFS population its only value is in migraine prophylaxis, for ;~hich it is excellent.
Dilantin: Useless in every CFS patient I have treated with it.
DHEA: Theoretically excellent, it is a neurosteroid which is a GABA antagonist, not necessarily a good thing for some patients. Ilopregnanolone should be the best neurosteroid (low in PMS).
Felbatrol: Not used much because of requirement for hematologic and LFT monitoring. Should be tried in every treatment-resistant patient. May work when nothing else does, especially for intractable headaches. It may cause headaches, however. There's no free lunch.
Gabitril: The only GABA reuptake inhibitor (like Prozac is a serotonin reuptake inhibitor). Very effective and very safe if you follow PDR dosing suggestions. Increase the dose too rapidly and the patient may get delirious or manic. Effects are reversible with flumazenil if necessary.
Gingko Biloba: Useful only for sexual dysfunction induced by serotonin reuptake inhibitors (SRIs). Inhibits platelet aggregation. Rare reports of brain hemorrhage. This adverse reaction raises the risk/benefit ratio.
Ginseng Saponins: Works a little like nitroglycerin, which converts to nitric oxide. Increases energy slightly.
Gotu Kola: A mild stimulant with no apparent adverse reactions.
Honey Bee Venom: As with any "natural product," bee venom has a multitude of ingredients. Patients should be skin tested for bee venom allergy first. Major constituents from my point of view are phospholipase A2 (PLPA2), which makes arachidonic acid, the precursor to elcosanoids (prostaglandins, leukotrienes, etc.), DA and NE. When it works, the patient often feels like he has been injected with rocket fuel. Effects last about one to two weeks. Has made three patients worse, two of whom were father and daughter. Patients should have an Epi-Pen (if available) and an antihistamine with them at all times. Plaquenil antagonizes PLLPA2. Arachidonic acid combines with effianolamine in the brain to make anandamide, an endogenous cannabinoid (like marijuana).
Hydergine: The most underused effective medication in the PDR. Extremely safe. A DA and Ach agonist. There is nothing else like it. Other dopamine agonists seem to be restricted in action to the nigrostriatal doparninergic tract, which is not important in CFS symptoms. Not the case with Hydergine, which is quite helpful for alertness, especially in those sedated by Baclofen. As with most medications listed, it can sometimes help all symptoms.
Kava-Kava: One of the two best "natural products" for CFS. May take up to eight weeks to have an effect. No ADRs (adverse drug reactions).
Ketamine: The best single agent for CFS/FMS and all other neurosomatic disorders. Known best as an NMDA receptor antagonist (the NMDA receptor is one of the several receptors for the excitatory amino acid glutamate), it increases dopamine in the limbic system, a very important objective in CFS. I administer it by slow intravenous infusion or in PLO gel for transdermal (through the skin) absorption. The intravenous route is more effective, but transdermal application can be done daily, and if effective, can obviate peaks and valleys and need for IVs. I have seen no cases of Ketamine abuse among my patients. Ketamine is one component of my "resurrection cocktail," for patients who have been bedridden for more than a year and whom I may only see once. The others are IV ascorbate (discussed in Betrayal), IV lidocaine, IV thyrotropin- releasing hormone (which raises all biogenic amines plus acetylcholine), Nimotop, and Neurontin (still the most effective oral agent but is being pushed by Tasmar). I am doing trials with Ketamme eyedrops.
Klonopin: The benzodiazepine to use if you are going to use one. Affects neurosteroid biosynthesis.
Kutapressin: I don't know how this drug works, but some patients have immediate symptomatic improvement after 2 ml IM. I don't usually prescribe it otherwise since there are so many immediate-acting options. It does increase bradykinin, and ADRs may be treated with drugs like Vosotec (ACE inhibitors).
Lamictal: One of the new anti-epileptic drugs (AEDs). All of them increase GABA, and most of them are N-methyl-d-aspartate (NMDA) antagonists. Works immediately. The main ADR is a rash, which can be minimized by gradual dosage escalations. Affects all symptoms. 50-100 mg of Larnictal and 800-1200 mg of Neurontin have rendered euthymic in 30 minutes every patient with acute manic excitement I have treated. Zyprexa and Rilutek could be added to this cocktail if necessary. Lamictal is also an antidepressant and may also work over four weeks or so.
IV lidocaine: In addition to its actions mentioned in Betrayal. it also acts as an NMDA antagonist. It is the second best treatment. I have given it about a thousand times without a serious ADR. Patients have come with great difficulty from other states or countries with the common lament of "If you can't help me I'm going to kill myself' (I hear this about twice a week). At least two patients, achieving complete symptomatic relief with IV lidocaine, returned home and could not find a physician or nursing service to administer it. Since they could not move to southern California, they were again bedridden and had to crawl to the bathroom. Not able to live this way any longer, they committed suicide, a worse outcome than the lidocaine toxicity, which never happens. Many physicians will not prescribe any of the medications I use, even if they help their patients a lot. Some medium-sized cities have not one physician who will care for CFS patients. I must treat them from afar, a hazardous practice medicolegally.
Marinol: Marinol-deta-9-tetrahydrocannobinoI is a medication I use rarely, because of the medicolegal implications. Among other things, it is a dopamine agonist in the limbic system (at the nucleus accumbens, a key structure in CFS), but an indirect one. It is also a calcium channel blocker. A few patients get total symptomatic relief with Marinol when one hundred other medications have failed. One such patient is applying for disability only because she cannot afford it. It is one of the last and best options for treating the diffuse pain of FMS, and is good for atypical facial pain. In five years it should be used routinely in many situations.
Methadone: Another drug I don't use very often, and for the same reason, although California has passed a law that physicians cannot be prosecuted for using opioids responsibly to treat chronic pain. Thus, it is less risky for me. Physicians in some states are afraid to prescribe it. It is the opioid of choice. Besides being an agonist at the mu opioid receptor, it is an NMDA receptor antagonist (like Ketamine), and blocks the serotonin transporter (like SRIs). I described its use as an antidepressant about 15 years ago in the medical literature. It is very cheap, does not produce much opioid euphoria, and often ameliorates all neurosomatic symptorils.
Nicotine Patch or Gum: I have been prescribing nicotine in these forms for a long time. Nicotine is analgesic, probably by virtue of its stimulating secretion of DA and NE. It binds to the nicotinic cholinergic receptor and can also have profound effects on mood, energy, and cognition. An occasional patient will have worsening of symptoms with nicotine.
Papaverine SA: Marketed many years ago as a vasodilator, this medication will probably be discontinued shortly. It is the only drug available that inhibits adenylate cyclase, thereby increasing cyclic AMP, which you may recall from biology class as being pretty important. There is an experimental antidepressant, rolipram, which has a similar mode of action. It preferentially affects energy, alertness, and cognition, and has very few ADRs. It is a top- 10 drug (cheap, too).
St. John's Wort (Hypericum): The other good "natural" remedy for CFS.
Tasmar (Tolcapone): Neither an exotic location on the Silk Road nor a Mafia-run turnpike in Chicago, Tasmar is a unique agent. It inhibits the enzyme catechol-ortho-methyltransferase (COMT), one of the two enzymes (monomine oxidase is the other) that metabolizes NE and DA. Tasmar degrades them in the synaptic cleft. I have been waiting for this drug for years. It is marketed for Parkinson's disease, and most physicians have not heard of it yet. It can work as monotherapy, either acutely or after four weeks or so. It may be more effective (immediately) when combined with a dopamine agonist such as Requip (quinpirole) or a reversible inhibitor of monoamine oxidase (RIMA) such as meclobemide, which due to the wisdom of the FDA is available in every other industrialized country in the world but the USA. The package insert advises against combining it with irreversible MAOIs such as Nardil and Pamate, so I have not done so. This combination would leave reuptake as the only mechanism to terminate the post-synaptic effect of catecholamines, although rats do quite well on the two drugs. Tasmar is in the top 10 ",Arith a bullet." An accountant, unable to work for three years, is back to work now on meclobemide and Tasmar. Adding Sinemet may enhance the action of Tasmar, since it is metabolized to dopamine. Sinemet may be given instead of Requip or Mirapex, or concomitantly. Requip and Mirapex are useful in that they are D3 agonists also. The D3 receptor is located primarily in the limbic system. Since COMT is a methyl group acceptor, it may work better by combining it with S-adenosylmethionine (SAMe), a methyl group donor with no ADRs, effective in FMS and depression. SAMe is available in many other countries, and certain buyer's clubs will supply you with it. Tasmar inactivates COMT, allowing SAMe to transfer methyl groups to precursors so that more norepinephrine can he formed. This process is termed "transmethylation" and is too complicated to discuss further in this column. Interested readers may consult the work of John R. Sinythies and R.J. Baldessarini and go from there.
Topamax: Another new AED, Toparnax has a little more affinity for the ANWA glutamate receptor, as well as the NMDA receptor. It has very few ADRs, and when it works, is quite energizing. Agonists at the third major class of glutamate receptor, the "metabotropic," of which there are of course various subtypes, are being developed as anxiolytics.
Viagra: I don't have enough money to buy stock in anything, but buying Pfizer a few months ago would have been almost as good as buying Microsoft in 1985. This drug works by inhibiting type 5 phosphodiesterase, one of the six known enzymes to degrade cyclic GMP (as important as cyclic AMP, but maybe not covered in biology class). Type 5 is supposed to be specific for the corpus cavemosurn of the penis and probably the clitoris as well. It is not all that specific, though, at least in my patients, who frequently experience flushing and headache. When Viagra works in CFS/FMS, patients experience a reduction in all symptoms. One patient whom I have been treating for 10 years had not responded to one medication until she took Viagra, whereupon she felt almost normal. Nitroglycerin and hydralazine, which stimulate cyclic GMP by different mechanisms, had not helped her.
Zyprexa: One of the new "atypical neuroleptics," with Risperdal and Seroquel, Zyprexa can he used as a sleeping aid, antidepressant, anxiolytic, and of special relevance to my practice, is probably the most effective treatment for borderline personality disorder. You can look up the symptoms in the DSM-IV, personality disorder.
There are many other current and pending treatments I have not touched on here, some of which are quite exciting. I shall discuss them in future columns and in my next book in a more scientific approach with longer discussions and references.
[Dr. Goldstein has published numerous times, is the editor-in-chief of a new medical monograph by The Haworth Medical Press, Medical Neuroimmunoendocrine Networks in Health and Illness, book reviewer for the Journal of Nervous and Mental Disease," as well as our medical advisor. He continues to work with treatmentresistant patients and his philosophy is not based primarily on making money but on "optimizing the health of each individual who consults me and teaching other health professionals to do the same." Dr. Goldstein may be reached at 701 N. Glassell St., Orange, CA 92867, Tel.: (714) 162830, FAX: (714) 516-2707.] 4
Have a great "energized" weekend.
Lanelle
If this has been posted before, feel free to delete it. Or maybe someone will pick up on something they've forgotten about.....
I got a real kick out of his Viagra comments....
Tiptoe Through The Treatments
A Brief Guide To Some of What's New Since
"Betrayal of The Brain"
By Jay A. Goldstein, M.D.
************************************
Acetyl-L-Carnitine Adderall Amantadine Ambien Aricept Baclofen Vitamin B12 BuSpar Clonidine Dexedrine Depakote Dilantin DHEA Felbatrol Gabitril Gingko Biloba Ginseng Saponins Gotu Kola Honey Bee Venom Hydergine Kava-Kava Ketamine Klonopin Kutapressin Lamictal IV lidocaine Marinol Methadone Nicotine Patch or Gum Papaverine SA St. John's Wort (Hypericum) Tasmar (Tolcapone) Topamax Viagra Zyprexa
**************************************
Acetyl-L-Carnitine: In theory, a good drug. It should work as an acetyl group donor to increase acetylcholine, and the camitine has already been shown to be effective in a double-blind experiment by the Drs. Plioplys. Acetyl-L-camitine also increases the levels of nerve growth factor (which are four times normal in the spinal fluid of FMS patients) and increases other transmitters like adenosine and ATP. In practice, a semi-dud.
Adderall: An amphetamine combination that a few patients find more energizing than plain dexedrine. Only about a third of CFS patients have a good response to stimulants, which act by squeezing doparnine (DA) and norepiniphrine (NE) out of neurons and glia. If these transmitters are much too low already, giving stimulants will ftirther lower the signal-to-noise ratio (STN) and increase symptoms.
Amantadine: A weak NMDA antagonist. HelpfW for a few patients. Doses higher than the PDR recommends may be more effective, but there is an increased risk of adverse drug reactions (ADRs) when exceeding this dose. Israelis have given 100 mg IV with good results in neurogenic pain. IV amantadine is not available in the USA. Amantadine, ketamine, dextromethorphan, and a new MNDA antagonist, memantine, can be used in trigger point injections as well as gel applications for local pain.
Ambien: The best sleeping pill. Does not cause dependence except in unusual circumstances.
Aricept: A cholinesterase inhibitor marketed for Alzheimer's disease. Has the advantage of once-a-day dosing and no requirement for liver function test (LFT). Does not work as well as Cognex, perhaps because it is not a potassium channel blocker. Cognex has several effects on neurotransmitters relevant to CFS/FMS.
Baclofen: A greatly under used medication. A GABA-B agonist with few ADRs, it has an immediate onset of action and is still in my top 10.
Vitamin B12: Besides being vital to transmethylation (which helps to synthesize NE), B12 2mg. orally in AM decreases inappropriate daytime melatonin secretion, thereby aiding in the treatment of the delayed sleep-wake cycle many CFS patients experience. Very large doses (10 mg) may aid transmethylation.
BuSpar: The ideal anxiolytic in all respects except efficacy. Best used as an SSRI augmentation agent, especially combined with Visen (not generic Pindolol). Augmentation strategies, of which there are many, do not work nearly as well in CFS as they do in major depression disorder.
Clonidine: Another greatly underused drug. Can be good for central pain, ADD, anxiety. Helps all symptoms in some patients. Eliminates nightmares. Safe and cheap. Comes in a patch that lasts all day. Better than Zanaflex, another alpha-2 agonist. Tolerance and depression have not been much of a problem. ADRs to clonidine can be reversed by yohimbine, an alpha-2 antagonist. Guanfacine (Tenex) is a less sedating alpha-2 antagonist with a 24-hour duration of action.
Dexedrine: An effective stimulant. Makes some patients calm also. May synergize with Ultram. Desoxyn may be better but has neurotoxicity. Many patients like Adderall more.
Depakote: In the CFS population its only value is in migraine prophylaxis, for ;~hich it is excellent.
Dilantin: Useless in every CFS patient I have treated with it.
DHEA: Theoretically excellent, it is a neurosteroid which is a GABA antagonist, not necessarily a good thing for some patients. Ilopregnanolone should be the best neurosteroid (low in PMS).
Felbatrol: Not used much because of requirement for hematologic and LFT monitoring. Should be tried in every treatment-resistant patient. May work when nothing else does, especially for intractable headaches. It may cause headaches, however. There's no free lunch.
Gabitril: The only GABA reuptake inhibitor (like Prozac is a serotonin reuptake inhibitor). Very effective and very safe if you follow PDR dosing suggestions. Increase the dose too rapidly and the patient may get delirious or manic. Effects are reversible with flumazenil if necessary.
Gingko Biloba: Useful only for sexual dysfunction induced by serotonin reuptake inhibitors (SRIs). Inhibits platelet aggregation. Rare reports of brain hemorrhage. This adverse reaction raises the risk/benefit ratio.
Ginseng Saponins: Works a little like nitroglycerin, which converts to nitric oxide. Increases energy slightly.
Gotu Kola: A mild stimulant with no apparent adverse reactions.
Honey Bee Venom: As with any "natural product," bee venom has a multitude of ingredients. Patients should be skin tested for bee venom allergy first. Major constituents from my point of view are phospholipase A2 (PLPA2), which makes arachidonic acid, the precursor to elcosanoids (prostaglandins, leukotrienes, etc.), DA and NE. When it works, the patient often feels like he has been injected with rocket fuel. Effects last about one to two weeks. Has made three patients worse, two of whom were father and daughter. Patients should have an Epi-Pen (if available) and an antihistamine with them at all times. Plaquenil antagonizes PLLPA2. Arachidonic acid combines with effianolamine in the brain to make anandamide, an endogenous cannabinoid (like marijuana).
Hydergine: The most underused effective medication in the PDR. Extremely safe. A DA and Ach agonist. There is nothing else like it. Other dopamine agonists seem to be restricted in action to the nigrostriatal doparninergic tract, which is not important in CFS symptoms. Not the case with Hydergine, which is quite helpful for alertness, especially in those sedated by Baclofen. As with most medications listed, it can sometimes help all symptoms.
Kava-Kava: One of the two best "natural products" for CFS. May take up to eight weeks to have an effect. No ADRs (adverse drug reactions).
Ketamine: The best single agent for CFS/FMS and all other neurosomatic disorders. Known best as an NMDA receptor antagonist (the NMDA receptor is one of the several receptors for the excitatory amino acid glutamate), it increases dopamine in the limbic system, a very important objective in CFS. I administer it by slow intravenous infusion or in PLO gel for transdermal (through the skin) absorption. The intravenous route is more effective, but transdermal application can be done daily, and if effective, can obviate peaks and valleys and need for IVs. I have seen no cases of Ketamine abuse among my patients. Ketamine is one component of my "resurrection cocktail," for patients who have been bedridden for more than a year and whom I may only see once. The others are IV ascorbate (discussed in Betrayal), IV lidocaine, IV thyrotropin- releasing hormone (which raises all biogenic amines plus acetylcholine), Nimotop, and Neurontin (still the most effective oral agent but is being pushed by Tasmar). I am doing trials with Ketamme eyedrops.
Klonopin: The benzodiazepine to use if you are going to use one. Affects neurosteroid biosynthesis.
Kutapressin: I don't know how this drug works, but some patients have immediate symptomatic improvement after 2 ml IM. I don't usually prescribe it otherwise since there are so many immediate-acting options. It does increase bradykinin, and ADRs may be treated with drugs like Vosotec (ACE inhibitors).
Lamictal: One of the new anti-epileptic drugs (AEDs). All of them increase GABA, and most of them are N-methyl-d-aspartate (NMDA) antagonists. Works immediately. The main ADR is a rash, which can be minimized by gradual dosage escalations. Affects all symptoms. 50-100 mg of Larnictal and 800-1200 mg of Neurontin have rendered euthymic in 30 minutes every patient with acute manic excitement I have treated. Zyprexa and Rilutek could be added to this cocktail if necessary. Lamictal is also an antidepressant and may also work over four weeks or so.
IV lidocaine: In addition to its actions mentioned in Betrayal. it also acts as an NMDA antagonist. It is the second best treatment. I have given it about a thousand times without a serious ADR. Patients have come with great difficulty from other states or countries with the common lament of "If you can't help me I'm going to kill myself' (I hear this about twice a week). At least two patients, achieving complete symptomatic relief with IV lidocaine, returned home and could not find a physician or nursing service to administer it. Since they could not move to southern California, they were again bedridden and had to crawl to the bathroom. Not able to live this way any longer, they committed suicide, a worse outcome than the lidocaine toxicity, which never happens. Many physicians will not prescribe any of the medications I use, even if they help their patients a lot. Some medium-sized cities have not one physician who will care for CFS patients. I must treat them from afar, a hazardous practice medicolegally.
Marinol: Marinol-deta-9-tetrahydrocannobinoI is a medication I use rarely, because of the medicolegal implications. Among other things, it is a dopamine agonist in the limbic system (at the nucleus accumbens, a key structure in CFS), but an indirect one. It is also a calcium channel blocker. A few patients get total symptomatic relief with Marinol when one hundred other medications have failed. One such patient is applying for disability only because she cannot afford it. It is one of the last and best options for treating the diffuse pain of FMS, and is good for atypical facial pain. In five years it should be used routinely in many situations.
Methadone: Another drug I don't use very often, and for the same reason, although California has passed a law that physicians cannot be prosecuted for using opioids responsibly to treat chronic pain. Thus, it is less risky for me. Physicians in some states are afraid to prescribe it. It is the opioid of choice. Besides being an agonist at the mu opioid receptor, it is an NMDA receptor antagonist (like Ketamine), and blocks the serotonin transporter (like SRIs). I described its use as an antidepressant about 15 years ago in the medical literature. It is very cheap, does not produce much opioid euphoria, and often ameliorates all neurosomatic symptorils.
Nicotine Patch or Gum: I have been prescribing nicotine in these forms for a long time. Nicotine is analgesic, probably by virtue of its stimulating secretion of DA and NE. It binds to the nicotinic cholinergic receptor and can also have profound effects on mood, energy, and cognition. An occasional patient will have worsening of symptoms with nicotine.
Papaverine SA: Marketed many years ago as a vasodilator, this medication will probably be discontinued shortly. It is the only drug available that inhibits adenylate cyclase, thereby increasing cyclic AMP, which you may recall from biology class as being pretty important. There is an experimental antidepressant, rolipram, which has a similar mode of action. It preferentially affects energy, alertness, and cognition, and has very few ADRs. It is a top- 10 drug (cheap, too).
St. John's Wort (Hypericum): The other good "natural" remedy for CFS.
Tasmar (Tolcapone): Neither an exotic location on the Silk Road nor a Mafia-run turnpike in Chicago, Tasmar is a unique agent. It inhibits the enzyme catechol-ortho-methyltransferase (COMT), one of the two enzymes (monomine oxidase is the other) that metabolizes NE and DA. Tasmar degrades them in the synaptic cleft. I have been waiting for this drug for years. It is marketed for Parkinson's disease, and most physicians have not heard of it yet. It can work as monotherapy, either acutely or after four weeks or so. It may be more effective (immediately) when combined with a dopamine agonist such as Requip (quinpirole) or a reversible inhibitor of monoamine oxidase (RIMA) such as meclobemide, which due to the wisdom of the FDA is available in every other industrialized country in the world but the USA. The package insert advises against combining it with irreversible MAOIs such as Nardil and Pamate, so I have not done so. This combination would leave reuptake as the only mechanism to terminate the post-synaptic effect of catecholamines, although rats do quite well on the two drugs. Tasmar is in the top 10 ",Arith a bullet." An accountant, unable to work for three years, is back to work now on meclobemide and Tasmar. Adding Sinemet may enhance the action of Tasmar, since it is metabolized to dopamine. Sinemet may be given instead of Requip or Mirapex, or concomitantly. Requip and Mirapex are useful in that they are D3 agonists also. The D3 receptor is located primarily in the limbic system. Since COMT is a methyl group acceptor, it may work better by combining it with S-adenosylmethionine (SAMe), a methyl group donor with no ADRs, effective in FMS and depression. SAMe is available in many other countries, and certain buyer's clubs will supply you with it. Tasmar inactivates COMT, allowing SAMe to transfer methyl groups to precursors so that more norepinephrine can he formed. This process is termed "transmethylation" and is too complicated to discuss further in this column. Interested readers may consult the work of John R. Sinythies and R.J. Baldessarini and go from there.
Topamax: Another new AED, Toparnax has a little more affinity for the ANWA glutamate receptor, as well as the NMDA receptor. It has very few ADRs, and when it works, is quite energizing. Agonists at the third major class of glutamate receptor, the "metabotropic," of which there are of course various subtypes, are being developed as anxiolytics.
Viagra: I don't have enough money to buy stock in anything, but buying Pfizer a few months ago would have been almost as good as buying Microsoft in 1985. This drug works by inhibiting type 5 phosphodiesterase, one of the six known enzymes to degrade cyclic GMP (as important as cyclic AMP, but maybe not covered in biology class). Type 5 is supposed to be specific for the corpus cavemosurn of the penis and probably the clitoris as well. It is not all that specific, though, at least in my patients, who frequently experience flushing and headache. When Viagra works in CFS/FMS, patients experience a reduction in all symptoms. One patient whom I have been treating for 10 years had not responded to one medication until she took Viagra, whereupon she felt almost normal. Nitroglycerin and hydralazine, which stimulate cyclic GMP by different mechanisms, had not helped her.
Zyprexa: One of the new "atypical neuroleptics," with Risperdal and Seroquel, Zyprexa can he used as a sleeping aid, antidepressant, anxiolytic, and of special relevance to my practice, is probably the most effective treatment for borderline personality disorder. You can look up the symptoms in the DSM-IV, personality disorder.
There are many other current and pending treatments I have not touched on here, some of which are quite exciting. I shall discuss them in future columns and in my next book in a more scientific approach with longer discussions and references.
[Dr. Goldstein has published numerous times, is the editor-in-chief of a new medical monograph by The Haworth Medical Press, Medical Neuroimmunoendocrine Networks in Health and Illness, book reviewer for the Journal of Nervous and Mental Disease," as well as our medical advisor. He continues to work with treatmentresistant patients and his philosophy is not based primarily on making money but on "optimizing the health of each individual who consults me and teaching other health professionals to do the same." Dr. Goldstein may be reached at 701 N. Glassell St., Orange, CA 92867, Tel.: (714) 162830, FAX: (714) 516-2707.] 4
Have a great "energized" weekend.
Lanelle
