Posted by SalArmy4me on August 29, 2001, at 1:24:25
In reply to MAOIs and safety, posted by IanSFO on August 29, 2001, at 0:22:34
1. American Journal of Nursing
Volume 100 January 2000 p 71
MAOI PRESCRIPTIONS: Way down, but still not out:
2. Shader, Richard I. MD. The Reappearance of a Monamine Oxidase Inhibitor (Isocarboxazid). Journal of Clinical Psychopharmacology. 19(2):105-106, April 1999.
3. Walker, SE. Tyramine Content of Previously Restricted Foods in Monoamine Oxidase Inhibitor Diets. Year Book of Psychiatry & Applied Mental Health. 1998(10):450-453, Annual 1998.
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#1 Amer. Journal of Nursing: "Only 2% of psychiatrists recently surveyed reported prescribing monoamine oxidase inhibitors (MAOIs) frequently. This is down from 25% 10 years ago, before the widespread use of selective serotonin reuptake inhibitors (SSRIs).The most common explanation for never or rarely prescribing MAOIs was potential interactions. Other reasons were side effects, a preference for other drugs, potential legal complications, the dietary restrictions required for patients receiving MAOIs, lack of training regarding their use, and lack of belief in their efficacy.
Meanwhile, the majority of respondents, 92%, acknowledged the usefulness of MAOIs for treating atypical depression, and a substantial percentage found them useful for major depression (melancholic type), panic disorder, social phobia, and other disorders. They are particularly useful for patients who don't respond to SSRIs and can't tolerate the side effects associated with tricyclic antidepressants.
MAOIs are prescribed infrequently, but it's important to be aware of their potential side effects (such as postural hypotension, insomnia, and headache) and the risk of hypertensive crisis with concomitant sympathomimetics, levodopa, and high-tyramine foods such as cheese, chocolate, wine, beer, and coffee."
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#2 Isocarboxazid: The Reappearance of a Monamine Oxidase Inhibitor (Isocarboxazid)
In 1988, we produced a monograph, MAOI Therapy. [1] We did so because of a noticeable trend toward a reemergence of the use of monoamine oxidase inhibitors (MAOIs) at a time when fewer physicians were exposed to them during training. Our goal in that monograph was to put their use in perspective so that prescribing could be done more safely and appropriately. Curiously, this trend toward more prescribing was short-lived. The successful introduction of fluoxetine and other serotonin transporter inhibitors shortly thereafter and the fact that moclobemide and brofaromine, highly touted reversible MAOIs, were not showing consistent utility in their phase 3 trials soon diminished the growing enthusiasm for MAOIs. It was not surprising then that Hoffmann-LaRoche withdrew their MAOI isocarboxazid (Marplan) from the market in 1994. Consistent with this, we have recently learned that another MAOI, nialamide (Niamid), was finally withdrawn by Pfizer from the French market where it was still available.We have had mixed feelings about this trend. When prescribed by appropriately trained physicians who understand their indications and safety concerns, the remaining U.S.-marketed MAOIs, phenelzine and tranylcypromine, have continued to provide relief to many patients who seem almost as if they are unique responders to MAOIs and who are willing to comply with curtailment of their diet.
We recently learned of the reintroduction of isocarboxazid to the U.S. market early in January 1999. Oxford Pharmaceutical Services acquired isocarboxazid and the use of the name, Marplan, from Hoffmann-LaRoche (Roche). Oxford is now marketing isocarboxazid, although Roche will continue to be the manufacturer of the drug, at least for the immediate future. We welcome the reappearance of isocarboxazid because there continue to be patients who fail to have an adequate response to whatever antidepressants we have available. From past experience, we can expect that there will be some patients for whom isocarboxazid provides unique benefit. In fact, a meta-analysis of intent-to-treat cohorts from three double-blind, placebo-controlled, published studies of isocarboxazid in outpatients showed a remarkably robust drug-placebo difference of 41.3% (+/- 18%). [2]
The reintroduction of isocarboxazid prompted us to look into some newer findings about MAOIs. For example, preclinical studies have shown that isocarboxazid and certain other MAOIs inhibit the binding of the dopamine agonist quinpirole to D2 receptors in brain. [3] This effect seems to be unrelated to any MAO inhibiting properties. Quinpirole, when given alone, causes a marked, dose-dependent attenuation of striatal c-fos (an immediate early gene) expression by serotonin agonists. [4] Finally, isocarboxazid and certain other irreversible MAOIs were found after long-term administration to decrease the density of I2 imidazoline-preferring receptors in rat brain as studied by the binding of labeled idazoxan. [5] Readers may recall that idazoxan is a potent [small alpha, Greek]2-adrenergic receptor antagonist. Unfortunately, the behavioral consequences of these effects of isocarboxazid and other MAOIs are not established. We were unable to find, for example, studies of these drugs in MAO knockout mice. Nevertheless, findings such as these suggest that any currently held mechanism of action concepts for MAOIs may be too limited or simplistic.
In recent years, the metabolism of isocarboxazid has become more clear. Rather than being metabolized by hepatic microsomal cytochromes or by hepatic acetylation, isocarboxazid is a specific substrate for and is hydrolyzed by RL2 hepatic microsomal carboxylesterase in rat liver microsomes. [6] Interestingly, this metabolizing enzyme is markedly induced by glucocorticoids and methylprednisolone. [7] This latter research convincingly demonstrated dose-dependent increased isocarboxazid hydrolase activity produced by dexamethasone. This finding may explain a clinical experience one of us (R.I.S.) had in the mid-1960s with a patient whose prednisone-induced anergic depression required increasing doses of isocarboxazid to maintain a positive clinical response even after discontinuation of the steroid. Finally, two simple and relatively sensitive spectrophotometric methods (using 7,7,8,8-tetracyanoquinodimethane as a [small pi, Greek]-electron acceptor) have been described to quantify isocarboxazid levels. [8]
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#3 MAOI Diet: Objectives.-To determine the tyramine content of various foods and beverages that have been restricted from the diets of individuals taking monamine oxidase inhibitors (MAOIs), but whose tyramine content is unclear or unknown, and to evaluate the effect of freshness on the tyramine content of some foods.Background.-Monoamine oxidase inhibitors are important in the treatment of refractory depressive illnesses, anxiety, and eating disorders. They have been associated with hypertensive crisis resulting from an interaction with foods containing tyramine. The list of restricted foods linked to hypertensive crisis has grown to more than 70 items. The danger of over-inclusive diets is that if a patient ingests a prohibited food and has no negative reaction, he or she may become careless and indulge in other restricted foods that may be more dangerous. The restricted foods and beverages have now been classified as containing high or low amounts of tyramine. The authors have received requests for information on specific foods for which there is little or no reliable information.
Methods.-The tyramine content of various foods and beverages was tested by liquid chromatography; 51 samples were tested, including samples of the inside and skin or peel of sausages and bananas.
Results.-Foods with dangerously high levels of tyramine include chicken liver aged 9 days, air-dried sausage, soy sauce, and sauerkraut (Table 1). No tyramine was found in Italian Chianti wine. Part-skim mozzarella cheese had extremely low amounts of tyramine. Although only one beer was analyzed and found to have small amounts of tyramine, alarmingly high amounts of tyramine were found in 4 tap beers in a previous report. This indicates that storage and hose contamination may encourage the production of tyramine. The pulp of bananas, even overripe bananas, had acceptable levels of tyramine. Raspberries contained low concentrations of tyramine.
Discussion.-The hypertensive response is variable and depends on many factors. Therefore, patients may be able to ingest 6 mg or more of tyramine and not have a response, but the danger of an increase in blood pressure is always present and may occur the next time a restricted food or beverage is ingested. The amount of ingested tyramine should remain below 6 mg. Most of the reported fatal and nonfatal hypertensive reactions associated with MAOIs have involved the ingestion of cheese. Although all aged cheese has traditionally been restricted, not all cheeses need be prohibited. Tap beer should be avoided. Foods that have been improperly stored or are spoiled may contain higher amounts of tyramine. Only foods with dangerously high levels of tyramine should continue to be restricted. All other foods are safe or safe in moderation. Patients should be given a diet that clearly identifies these two groups of foods. These findings should be combined with findings from similar studies to develop accurate and comprehensive lists of foods that must be absolutely restricted for these individuals.
Psychiatric practitioners who use monoamine oxidase inhibitors are all familiar with the "white-knuckle" approach to treating those patients. Since the selective MAO-A inhibitors failed to make it to the marketplace, we still have to rely on these old agents at least occasionally. This article nicely revisits the issue of tyramine content as a risk factor in the MAOI diet restriction. Psychopharmacologists almost uniformly attest to the effectiveness of these agents for patients who have failed standard treatments. This article gives objective information about the danger of many foods that we have advised patients to avoid. (I have never had any patients, by the way, who ate banana peels.) This article should allow many of us to modify our food restriction lists and the advice we give to patients. It is also probably worth noting that the explosion of "microbreweries" creating new beers every week will continue to make our lives interesting. Caution is probably indicated until we have information about these newer brews (which we are not likely to get any time soon). This report is a useful clinical article for practitioners and patients who already have enough problems on their plate (pun intended)."
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The final chord of help
was the finger of the Almighty
as He split the veil of separation
to allow me into His presence.The symphony of love
was played to perfection
by hands that stretched though time
to heal my shattered life.
--Lt. Rachel Messer, Salvation Army Central Territory
poster:SalArmy4me
thread:76778
URL: http://www.dr-bob.org/babble/20010828/msgs/76782.html