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Monoamine Oxidase Inhibitors Ronald A. Remick, MD, FRCPC Colleen Froese, MD Monoamine Oxidase Inhibitors: Clinical Review SUMMARY RESUME Monoamine oxidase inhibitors (MAGIs) are Les inhibiteurs de la monoamine-oxydase sont efficaces comme antidepresseurs. On les utilise de effective antidepressant agents. They are plus en plus efficacement dans un certain nombre increasingly and effectively used in a d'autres syndromes medicaux tant psychiatriques number of other psychiatric and que non psychiatriques. Leur potentiel toxique (i.e. non-psychiatric medical syndromes. Their reaction hypertensive) semble moindre que ne le potential for serious toxicity (i.e., laissaient supposer les rapports originaux, et de nouveaux substrats specifiques aux IMAO semblent hypertensive reaction) is far less than presenter encore moins de toxicit. L'auteur revise la original reports suggest, and newer pharmacologie, le mecanisme d'action, les indications reversible substrate-specific MAOIs may offer cliniques et les strategies permettant des posologies even less toxicity. The author reviews the appropriees aux IMAO. On en decrit les effets pharmacology, mechanism of action, clinical secondaires les plus frequents (hypotension, gain strategies of ponderal, dysfonction sexuelle, insomnie, sedation indications, and dosing MAOIs. diurne, myoclonie et episodes hypertensifs) et on en The common MAOI side-effects propose le traitement approprie. On y decrit (hypotension, weight gain, sexual egalement les developpements cliniques recents dysfunction, insomnia, daytime sedation, entourant les IMAO. myoclonus, and hypertensive episodes) are described and management techniques suggested. Recent clinical developments involving MAOIs are outlined. (Can Fam Physician 1990; 36:1151-1155.) Key words: antidepressants, family medicine, monoamine oxidase inhibitors, mood disorders, pharmacologic agents, psychiatry _ 4 ._1 Dr. Remick is an Associate clinical interest in MAOIs because of a Efficacy Professor and Assistant Head, number of factors. Early studies, which suggested that Department of Psychiatry, 1. More critical reviews of earlier stu- MAOIs are less effective than tricyclic University of British Columbia, and dies, coupled with recent research on antidepressants,' were not methodolog- is Director, Mood Disorders Service, MAOI efficacy, suggest that they are ef- Department of Psychiatry, fective antidepressants. ically sound and have been critiqued.' University Hospital, University of 2. Monoamine oxidase inhibitors could Recent trials with tranylcypromine and iso- British Columbia Site, Vancouver. have a broader range ofactivity thanjust (Parnate), phenelzine (Nardil), Dr. Froese is a Resident in depressive syndromes, which could carboxazid (Marplan) provide evidence Psychiatry, Department of then extend their use in the medical that these drugs are superior to placebo Psychiatry, University of British and equivalent or superior to tricyclics Columbia, Vancouver. Requests for community. 3. There is a growing awareness that in depressed patients.-6 All recent stu- reprints to: Dr. R.A. Remick, dies indicate that MAOIs are effective in Assistant Head, Department of these drugs are less toxic than previous reports suggest. a variety of depressive states, although Psychiatry, University Hospital, depression with associated features of UBC Site, 2255 Wesbrook Mall, 4. Newer, more specific and perhaps Vancouver, B.C. V6T 2A1 less toxic MAOIS may further increase anxiety, somatization, and hypochon- their safety and spectrum of activity. driasis (the so-called atypical depres- -9 ONOAMINE OXIDASE inhibi- With these factors in mind, this clinical- sions) seem particularly responsive.37 IlVXtors have been marketed as anti- ly oriented review is intended to evalu- In addition to their use in major de- depressants for 30 years,' yet are used ate new developments and to reacquaint pression, MAOIs have been used suc- infrequently. There is now a renewed physicians with MAOIS. cessfully in a variety of other disorders, CAN. FAM. PHYSICIAN Vol. 36: JUNE 1990 1151 including panic attacks, panic disorders whether this directly results in their an- cult to manage on MAOIS. Patients with and agoraphobia,8'0 obsessive-compul- tidepressant effect as originally hypoth- substance or alcohol abuse or who can- sive disorder," social phobia,'2 esized. not responsibly comply with dietary re- post-traumatic stress syndrome, buli- The antidepressant effects are known strictions should not receive MAOIS. Re- mia,' attention deficit disorders,'4 to be less likely to occur when peripher- cent work suggests that patients receiv- chronic pain syndrome,'5 narcolepsy, al monoamine oxidase inhibition is less ing fluoxetine should discontinue this Parkinson's disease, and migraine than 75%.2° Comments concerning how drug for five weeks before initiating headaches. 16 MAOIS work in depression (or other psy- MAOI treatment.23 chiatric syndromes) must be considered Pharmacology speculative. Recent theories postulate Dosing Brain monoamine oxidase is located that the accumulation of monoamine After deciding to use an MAOI, the pa- presynaptically and oxidatively deami- neurotransmitters due to monoamine tient should be instructed to observe the nates a wide variety of monoamines, in- oxidase inhibition leads to either pre- or food, drink, and drug restrictions for at cluding the putative monoamine neuro- post-synaptic receptor changes that re- least 24 hours before starting the first transmitters (noradrenaline, dopamine, sult in their psychoactive effects.2' 22 dose and for two weeks after stopping serotonin) and a variety of monoamines the last dose (Chart 1). Doses less than found in foodstuffs (tyramine, phenele- Clinical Use thylamine). 16 Before starting a patient on MAOI Chart 1 In the 1 950s, iproniazid, a drug tested therapy, the following questions should Instructions for Patients Taking for its antituberculous activity, was be answered. Monoamine Oxidase Inhibitors found to have mood-elevating proper- 1. Does the patient have a disorder that Foods to avoid ties.'7 Later, it was discovered this ef- will respond to MAOI treatment? Evi- * Cheese (cottage cheese, ricotta, fect was from the MAOI properties ofthe dence suggests that patients with a ma- and cream cheese are permitted). Be- drug, and research into less toxic MAOIS jor depressive disorder, and especially ware of pizza, fondues, many Italian began. Currently available MAOIS in the depressive states associated with anxi- dishes, and salad dressings United States ety, panic attacks, or agoraphobia, will . Red wine and sherry and Canada are phenel- * Smoked or pickled fish (especially zine, tranylcypromine, and isocarboxa- respond to an MAOI. If the patient war- herring, lox, anchovies, and caviar) zid. Phenelzine and isocarboxazid are rants antidepressant therapy, consider * Dry sausage (pepperoni, salami, hydrazine compounds; tranylcypro- MAOIS. They may be the treatment of bologna, summer sausage) mine is not. choice for patients who do not respond * Aged meats (chicken or beef pate, Two forms of brain monoamine oxi- to tricyclic agents or for patients who corned beef dase are now recognized, and they are are intolerant of tricyclic antidepres- * Fava or broad bean pods classified as type A or type B, according sants. Symptoms of atypical depres- * Yeast vitamin supplements (brew- to substrate specificity. Monoamine A sion, including anxiety, somatization, er's yeast) acts upon the following substrates: ser- hypersomnia, hyperphagia, and lethar- * Meat extracts (Bovril, marmite, soup otonin, epinephrine, norepinephrine, gy, may respond preferentially to cubes, and soups with meat extracts) In general, avoid all foods that may normetanephrine, octopamine, tyra- MAOIs. be slightly off, fermented, aged, mine, and dopamine. Monoamine B se- 2. Will the patient comply with diet and or leftovers. lects benzylamines, phenelethylamine, drug restrictions? The willingness of Do not use cold decongestants, N-methylhistamine, tyramine, and do- the patient to follow strict dietary con- hayfever, or sinus remedies (i.e., pamine. All currently marketed MAOIS trol (Chart 1) should be determined. Of- Dristan, Sudafed, Sinutab, Con- are non-selective with to A or B ten meal on other tac C, Coricidin "D," Neo-syneph- respect preparation depends rine nose drops, Novahistine) substrates, but newer MAOIS currently family members; any MAOI dietary dis- containing pseudoephedrine, under investigation are A- or B-specific. cussions must include the preparer of phenylephedrine, and phenylpro- Selective monoamine oxidase A inhibi- family meals. Involvement by family panolamine. Be sure to tell your tors are superior antidepressants com- members will also improve the patient's physician, surgeon, and dentist pared with selective monoamine oxi- and you are taking this medication. drug dietary compliance. Other medications to avoid are dase B inhibitors.'8 3. Are there any potential advantages to antihypertensive agents (methyl- All clinically available MAOIs are ir- selecting an MAOI for some patients? dopa, guanethidine, reserpine), reversible in their binding to mono- Patients with cardiac problems, espe- narcotics (meperidine), sympa- amine oxidase. Enzyme resynthesis, cially conduction defects, which require thomimetics (dopamine, metara- which has been estimated to occur with caution with could be minol), anesthetic drugs, and in- tricyclic agents, sulin. Do not use diet pills (am- a half-life of 10 to 12 days in the brain, treated with MAOIS. Patients with hy- phetamines)
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