Original Author: Paul Perry, Ph.D, BCPP
Latest Revisers: Paul Perry, Ph.D, BCPP, Brian C. Lund,
Pharm.D.
Creation Date: 1996
Last Revision Date: March 2001
Peer Review Status: Internally Peer Reviewed
In the age of SSRIs, monoamine oxidase inhibitors (MAOIs) have a limited role. MAOIs have been used as an alternative to TCAs in patients with second degree bundle branch block. With the multitude of SSRIs and second generation antidepressants available, MAOI prescribing is generally limited to refractory depression. However, in patients who are doing well on an MAOI and have adjusted to the lifestyle modifications, there is not necessarily any reason to switch to a newer agent. After all, the limited use of MAOIs is not due to a lack of efficacy, but to the myriad of adverse effects associated with the use of these agents. Therefore, an understanding of these adverse effects is essential in the use of MAOI antidepressants.
PREVALENCE
Rabkin et al (1984) compared the prevalence of 14 major ADRs of phenelzine and tranylcypromine with the TCA, imipramine and placebo in a structured retrospective chart review. The ADR reporting consisted of the physician asking the patient in an open-ended fashion if they were experiencing any adverse effects. For an ADR to be documented it had to be reported by the patient, noted by the physician, and identified by the rater. This method, opposed to using a checklist format, tends to under report ADRs. Significant differences in risk for major ADRs, as well as distinctive ADR profiles for each drug were observed. Most ADRs occurred for phenelzine, but these did not result in more frequent discontinuation of the drug than with tranylcypromine, nor were they accounted for by differences in age, sex, diagnosis, or duration of treatment. Mean maximum doses prescribed were 269 + 68 mg/d for imipramine, 69 + 22 mg/d for phenelzine, and 50 + 15 mg/d for tranylcypromine. Table 1 below lists the prevalence of the ADRs for the four groups.
Robinson et al (1982) estimated the incidence of phenelzine side effects in 85 patients treated with 60 mg/day for 6 weeks. Patients completed a side effect checklist initially and biweekly for the duration of the study. The patients experienced 2.7 side effects per patient. Table 2 demonstrates the distribution of these ADRs compared to amitriptyline 150 mg/d.
Table 3 reflects the relative likelihood of the MAOIs causing the following ADRs. These comparisons are based upon Sheehan's et al (1980-81) clinical experience.
ALLERGIC
The majority of the allergic or idiosyncratic reactions with the MAOIs occurred when the drugs were introduced onto the market in the early 60's. Skin rashes, primarily maculopapular, are still occasionally reported. The allergic reactions of red/green blindness with optic atrophy and hepatotoxicity led to the removal of the causative agents, pheniprazine and iproniazid, respectively. These reactions are rarely reported with the currently available MAOIs (Sheehan et al 1980-81).
CARDIOVASCULAR
EKG. Robinson et al (1982) studied the EKGs and blood pressures of 45 depressed outpatients receiving phenelzine 60 mg/day over a 6 week period. Baseline and 6-week standard 12-lead EKGs were obtained and mean baseline and treatment values were reported. Heart rate significantly decreased from 73 to 67 beats per minute and the corrected QT interval decreased from 432 msec to 413 msec. The PR interval and QRS complex were not affected. The decrease in the pulse is believed due to a sympatholytic action of MAOIs. This effect was in opposition to that observed with the TCA amitriptyline. Patients receiving amitriptyline 150 mg/day experienced a mean QT interval prolongation from 430 msec to 449 msec. This data supports the use of MAOIs as an alternative to TCAs in patients with second degree bundle branch block.
Blood Pressure. Robinson et al (1982) also examined effects of phenelzine on blood pressure. Pressures were recorded in the supine position and then repeated within 30-60 seconds in the upright position. A postural effect was seen as the mean fall in systolic blood pressure at week 6 was 12 mm Hg and the mean decrease in diastolic blood pressure was 7.7 mm Hg. In addition, phenelzine exerted an effect on resting blood pressure. The mean sitting blood pressure fell from a baseline of 125/81 to 117/77 at week 6. Therefore, it appears that MAOIs have a primary antihypertensive effect in addition to an orthostatic effect. Patients over 50 years of age were more likely to experience a greater decline in standing and sitting BP than younger patients. A significant negative correlation was found between percent of MAO inhibition and both standing and supine blood pressures.
Kronig et al (1983) investigated the onset of blood pressure effects of phenelzine 50-70 mg/d, over five weeks in 14 patients. Two (14%) patients developed severe orthostatic hypotension. The weekly mean orthostatic drops were: week 1 - 2 mm Hg, week 2 &endash; 5 mm Hg, week 3 &endash; 7 mm Hg, week 4 &endash; 12 mm Hg, and week 5 &endash; 9 mm Hg. The maximal effect of phenelzine on orthostatic hypotension was not observed until 4 weeks after initiation and then seemed to level off.
Therefore, blood pressure effects of phenelzine apparently differ from tricyclics in that (1) phenelzine affects both lying systolic blood pressure and the orthostatic drop, and (2) the blood pressure effects of phenelzine have a slower onset, maximize at four weeks and then appear to plateau or potentially decrease in intensity.
MAOIs probably affect cardiovascular function largely through a central adrenergic and/or sympathetic ganglionic effect (Robinson et al 1982). Inhibition of sympathetic tone by MAOIs would account for many of the observed effects on heart rate, QT interval and blood pressure. Since there is a correlation between dose and occurrence, reducing the dose is helpful in alleviating the problem. Increased divided doses during the day or single daily dosing at bedtime may also be beneficial. Contributing factors that ought to be ruled out apart from the MAOI as the cause include dieting, low salt diet, dehydration, concomitant use of either diuretics or antihypertensives, or endocrinopathies, i.e. hypothyroid or hypoadrenal states. Potentially useful ancillary treatments include salt tablets 600-1800 mg po bid for 8 weeks and then reduction of the intake or fludrocortisone (Florinef) 0.3-0.6 mg/d for 4 to 6 weeks. It is well to remember that steroid usage carries the adverse reaction potential for edema, hypervolemia, hypokalemia, and congestive heart failure (Rabkin et al 1985)
The orthostatic hypotensive effects of the MAOIs appear in the majority of patients to resolve and are surprisingly replaced by significant but asymptomatic and transient increases in blood pressure. Keck et al (1989) found that both the sitting systolic and diastolic blood pressures were significantly increased at hours 1 and 2 but returned to baseline at hours 3 and 4 after the administration of either tranylcypromine (n=12), phenelzine (n=5), or pargyline (n=1). These patients had been taking MAOIs chronically for greater than one month. Although none of the patients were symptomatic, 56% (10/18) of the patients experienced a systolic blood pressure elevation of ³ 20 mm Hg while 33% (6/18) experienced a similar diastolic blood pressure elevation. There were no significant differences in the sitting and standing pressures and pulses of these patients.
Hypertensive Crisis. Ingestion of monoamine oxidase inhibitors (including selegilene (L-deprenyl)) (McGrath et al 1989) and foods containing certain pressor amines or proprietary drugs containing sympathomimetic agents have been associated with potentially serious hyperadrenergic states. The interaction is characterized by severe occipital and temporal headache, diaphoresis, mydriasis, elevation of both systolic and diastolic blood pressures, neck stiffness, and neuromuscular excitation generally occurring within two hours of ingestion of the food or drug. Although rare, cardiac dysrhythmias, heart failure, or intracerebral hemorrhage can occur.
A retrospective analysis of the incidence of acute hypertensive crisis in 692 patients treated with MAOIs found that the incidence was 8.4% prior to instituting dietary restrictions but 3.3% after dietary restrictions were imposed (Bethune 1964). In the Rabkin chart review (1985) study, 11 patients (8%) on phenelzine and one patient (2%) taking tranylcypromine experienced hypertensive reactions.
Tyramine is the pressor amine most often implicated in these reactions. It is produced by decarboxylation of tyrosine, which is derived from protein. Tyramine exerts its pressor action by releasing norepinephrine from the storage sites at nerve endings. The pressor action is potentiated in patients on MAOIs because there will be a greater amount of norepinephrine present at the nerve ending due to MAO inhibition. In two patients, Horowitz et al (1964) reported that 6 mg of tyramine caused a moderate rise in blood pressure although the patient remained asymptomatic, while in another patient 28 mg of tyramine contained in 20 g of cheddar cheese caused a headache in conjunction with the rise in blood pressure. Ten mg may exhibit a marked pressor effect (Sjoqvist 1965) and 25 mg can produce a severe hypertensive crisis (Stewart 1976). The oral tyramine pressure test has shown that 8 mg of tyramine elevates systolic blood pressure by 30 mm Hg in 50% of subjects (Bieck and Antonin 1988). Other amines and amine precursors such as histamine, dopamine, levodopa, and tyrosine may also be involved in these reactions (Raisfeld 1972). Sympathomimetics such as amphetamines, methylphenidate, ephedrine, pseudoephedrine, phenylpropanolamine, and phenylephrine have been reported to interact with MAOIs (Ponto et al 1977).
Cheeses are the foodstuff most commonly reported to precipitate hypertensive crisis with MAOIs (67 of 80 reported cases, 84%). Reactions with certain alcoholic beverages (5 of 80 cases, 6%) and yeast products have also been reported (Stewart 1976, Ponto et al 1977). However, not all types of cheese contain significant amounts of tyramine to cause this adverse reaction. As a general rule, any protein-containing food that has undergone degradation may present a hazard. Therefore, non-matured cheeses such as cottage cheese, processed slices, ricotta and cream cheese are safe, as these contain little or no tyramine. As long as fresh milk products such as sour cream, yogurt, and ice cream are stored properly, these items may be consumed by patients taking MAOIs (Gardner et al 1996). It is now recommended that no more than two domestic bottled or canned beers or 4-fl-oz glasses or red or white wine per day, this includes nonalcoholic beer. High tyramine concentrations have been reported in four tap beers, which suggests that storage and contamination of the hose from the keg to the tap may provide conditions leading to the production of tyramine (Walker et al 1996). Yeast/protein extracts occasionally found in packet soups, as well as yeast vitamin supplements (Brewer's Yeast, Marmite) and are to be avoided, whereas baker's yeast contained in baked goods is safe. Unacceptable meats and fish include smoked or pickled fish (herring) and shrimp paste, caviar, beef or chicken liver, and fermented sausages (bologna, pepperoni, salami, summer sausage). Improper storage of any meat can lead to an environment where tyramine will increase, for example in chicken livers, see table 5. Once restricted fruits and vegetables include avocados, canned or overripe figs and stewed whole bananas/banana peel, these appear to be relatively safe if not over consumed see table 5 (Gardner 1996). Products containing fermented bean curd (soya beans, soya paste, soy sauce) contain large amounts of tyramine (Walker et al 1996).
There are a number of non-tyramine containing foods that are not permitted. Broad beans also known as Fava or Italian broad beans, which contain dopamine, are not allowed while the other shelled beans such as lima beans and string beans are permitted. Large amounts of caffeine can have sufficient pressor activity to cause problems. Chocolate may yield harmful amounts of tyramine and phenylethylamine, a weak pressor agent, if ingested in large amounts. Some Ginseng containing products have caused headache, tremors, and manic-like symptoms (Anonymous 1989). Mono-sodium glutamate (MSG) has been associated with complaints of headaches and palpitations (Gelenberg 1988). Table 4 provides a list of cheeses and their tyramine content. Table 5, 6 and 7 illustrate the tyramine content in various foods as well as in table 7 a table of those foods that should be avoided vs those restrictions which are unnecessary. It takes only a small quantity of cheese but a large quantity of wine or beer to precipitate a hypertensive crisis (Shulman et al 1989). After a patient discontinues the MAOI antidepressant it is recommended that the tyramine-free diet be continued for at least a month (Bieck et al 1989).
Hypertensive Crisis Management. Clary and Schwizer (1987) reported two cases of MAOI hypertensive crisis that were successfully treated with sublingual nifedipine capsules. Following two cheese/MAOI interactions two patients chewed then swallowed nifedipine, 10 mg SL. Within seven to ten minutes the diastolic blood pressures had decreased from 120 and 112 mm Hg to 96 and 84 mm Hg respectively. Golwyn and Sevlie (1993) described their 4 year experience with MAOI antidepressants (n Å 360) and nifedipine. The hypertensive crisis rate despite "intense and continuous" patient education was still 8%. In all 29 cases of hypertensive crisis, the nifedipine was rapidly effective and no ADRs were noted even when the nifedipine was taken for the wrong reasons. No patient noted a rapid remission of the headache unless and until the nifedipine was taken. The antihypertensive effect lasts 4-6 hours. While the use of sublingual nifedipine in this setting has been reported to be reasonably safe, the general practice of sublingual nifedipine for hypertensive emergencies has been strongly challenged (Grossman et al 1996). The authors of this review/editorial site numerous reported cases of serious, even fatal complications of sublingual nifedipine use. Coupled with the lack of any clinical documentation attesting to a benefit, the authors argue that the use of sublingual nifedipine be abandoned. Therefore, when patients taking an MAOI experience a severe headache, especially when they've recently been non-compliant with their diet, they should report to the emergency room to receive appropriate hypertensive crisis management.
Rabkin et al (1985) suggest that the most effective form of prophylaxis is to convince the patient that dietary adherence is mandatory. Informed consent phrased in the following terminology is also recommended, i.e. "a medically serious side effect can occur after eating the wrong food or taking medicines that are on the restricted list...it starts with palpitations, severe headaches and increase in blood pressure. If severe and not treated, it is conceivable that a stroke could develop." Written patient information such as the MAOI monograph in the Psychotropic Drug Handbook ought to be given to the patients as well.
HEPATIC
Hepatic injury caused by the MAOIs is characteristically hepatocellular and has the potential to progress to severe liver necrosis. These hepatic injuries are usually caused by the hydrazine MAOIs, i.e., phenelzine and isocarboxazid. Current evidence suggests that hydrazine-linked liver damage results from a toxic metabolite that is generated in rare susceptible individuals. It is hypothesized that the toxicity may be related to the patients acetylator phenotype. Women and the elderly may be more susceptible. The toxicity presents as an acute or subacute hepatic necrosis with varying degrees of cholestasis after 1-6 months of treatment with symptoms that include anorexia, weakness, malaise, and jaundice of an insidious onset. The bilirubin is elevated, AST and ALT are 8-10 times normal, and the alkaline phosphatase is only slightly elevated. A bilirubin of > 20 mg % is a bad prognostic marker. Fatalities occur in one in 5 effected patients (Zimmerman and Ishak 1987).
NERVOUS SYSTEM
CNS ADRs secondary to pyridoxine deficiency can result in peripheral neuropathy, ataxia, hyperacusis, hyperirritability, depression carpal tunnel syndrome and in extreme cases seizures, coma and death. Stewart et al (1984) reported six cases of pyridoxine deficiency secondary to phenelzine and "electric shock" sensations. All the patients had low pyridoxine levels and all symptoms responded to pyridoxine 150-300 mg/d within several weeks.
MAOIs are known to produce neuromuscular effects at therapeutic and toxic doses that range from muscle tension and muscle twitches in their mild form to forceful myoclonic jerks. Lieberman et al (1986) hypothesize that these ADRs are the result of the MAOIs producing a condition of heightened neuromuscular excitability due to a combination of increased serotonergic tone and central disinhibition of a-motor neuro-mediated spinal activity.
In the Rabkin studies (1984, 1985) anorgasmia and/or impotence was the most common ADR seen with phenelzine. It occurred at a median dose of 75 mg/d after 7 to 8 weeks of treatment and was significantly more common in the male patients. As Table 1 suggests it occurred significantly more often with phenelzine than tranylcypromine. For some patients this adverse effect abates over time. Dose reduction is helpful for some patients, while for others the use of cyproheptadine 1-4 mg at bedtime has been effective (DeCastro 1985). Additionally, ejaculatory dysfunction might be responsive to bethanecol (Urecholine) 10 mg 30 minutes prior to sexual activity (Segraves 1987). This treatment has been successful for imipramine-induced ejaculatory dysfunction.
Phenelzine and tranylcypromine have been reported to cause severe daytime drowsiness in a small number of patients. Use of caffeine and vigorous exercise were not helpful. It is noted to be transient but only after months of being on the drug. It is suggested that hypersomnolent bipolar depressed patients seem to be at the greatest risk. The substitution of isocarboxazid is effective in some patients (Teicher et al 1988). On the other hand, MAOI-induced insomnia is estimated to occur in 4-17% of patients. Trazodone 50-200 mg/d was effective in treating this problem in 12 of 13 affected patients (Nierenberg and Keck 1989).
PSYCHIATRIC
"Switching" from depression to mania similar to that observed with the TCAs also may occur with the MAOIs. Fourteen of 141 patients (10%) treated with phenelzine, three of 41 patients (7%) treated with tranylcypromine, and none treated with imipramine or placebo became hypomanic in the Rabkin series (1985). The data showed a trend for bipolar patients to be more likely than nonbipolar patients to develop hypomania on MAOIs. The association approached significance for phenelzine and was significant for tranylcypromine and also for all the MAOIs combined. Management suggests either MAOI dose reduction or lithium augmentation after-the-fact or lithium prophylaxis before-the-fact when using the MAOIs in bipolar patients or patients with positive bipolar family histories (Rabkin et al 1985). Bowden et al (1989) reported two "switch" cases in unipolar depressed patients treated with phenelzine who had greater than 80% platelet MAOI. The mania resolved on decreasing the dose such that the % MAO inhibition was less than 80%.
WITHDRAWAL REACTIONS
Many articles on the clinical use of MAOIs do not mention any problems concerning the abrupt withdrawal of MAOIs in patients. However, two recent reports have suggested there may indeed be a problem. Joyce and Walshe (1983) described two patients who abruptly discontinued their phenelzine dose, i.e. 45 mg/d for 7 years and 90 mg/d for 5 months and experienced vivid and frightening dreams for the next two to ten nights. Palladino (1983) describes a patient receiving phenelzine 60 mg/d for 6 months who abruptly discontinued her medication. This withdrawal reaction was quite severe. The patient experienced muscle weakness, tremulousness, "hot and cold" feelings, paresthesias, diaphoresis, shivering, and frontal lobe headache starting 24 hours after discontinuation. On the second night the vivid and frightening nightmares began. The patients restarted phenelzine on day 4. Although the nightmares recurred that night all the withdrawal symptoms had abated within 24 hours after restarting the drug. The patient was later tapered off phenelzine over a two week period without incident. Liskin et al (1985) described two patients who became organic on discontinuation of phenelzine. In addition to the delirium, one patient became catatonic while the other patient experienced hallucinations and delusions. These reports thus suggest that tapering the MAOI is a reasonable precaution especially in outpatients. However, this reaction occurs infrequently and routine tapering is probably not necessary, especially when the goal is to start another class of antidepressants. It is more reasonable to abruptly stop the MAOI and restart if hallucinations or other withdrawal symptoms occur. In these patients a taper over several days in inpatients and 2 weeks in outpatients would be reasonable.
SWITCHING MAOIs
Sheehan et al (1980-81) have recommended that when switching from one MAOI to another at least a one week drug free interval is advisable. Although the rationale for the advice is elusive, its wisdom is based on empiric grounds. Gelenberg (1984) described two patients, who because of ADRs in one and lack of response in the second, were switched from phenelzine to tranylcypromine without any drug free period. One patient experienced a stroke and the other a hypertensive crisis. True et al (1985) report a case of switching a patient without incident although they still recommend to be absolutely safe the patient ought to be "washed out" of one MAOI for at least ten days prior to starting the new MAOI.
MAOI/TCA ANTIDEPRESSANT INTERACTIONS
The therapeutic combination of monoamine oxidase inhibitors and tricyclic antidepressants is widely considered to be potentially lethal. Many sources suggest that concurrent therapy with these agents is contraindicated. Reports that the combination of an MAOI plus a TCA tends to produce hyperpyrexia, restlessness, seizures, muscle twitching, and even death have lead to the recommendation that a washout period of 14 days is necessary when switching a patient from a TCA to an MAOI or vice versa. Recently, however, informed opinion has shifted from an absolute contraindication to a cautious recommendation for the combination. The simultaneous administration of these agents is potentially efficacious and safe if carefully monitored and controlled.
Three mechanisms for this interaction have been proposed (Loveless and Maxwell 1965)
The third mechanism appears most valid because, unlike the first, it accounts for the difference between the toxic reactions encountered in a single- entity and combination drug overdose cases. For example, death from an overdose of imipramine stems from respiratory depression with only a mild hyperpyrexia (approximately 1°C), whereas death after administration of the combination of an MAOI and imipramine stems from hyperpyrexia in rabbits (Loveless and Maxwell 1965). The hyperpyrexic response observed from the combination of an MAOI and a TCA are due to the increased brain amine levels caused by the MAOI and the more selective inhibition of the reuptake of norepinephrine resulting in enhanced levels of norepinephrine in the brain. This third mechanism also explains the increased cardiovascular toxicity of the combination due to the augmentation of the pressor effect of norepinephrine (Risch et al 1982).
The co-administration of a TCA and MAOI may not be as hazardous as previously thought if several guidelines are followed: 1) begin the two together (within a day or two of each other), start with low doses and gradually increase the dose of both together 2) for the TCA use amitriptyline, trimipramine or doxepin and 3) avoid imipramine (Graham et al 1982).
MAOI AND ECT
It has been suggested to allow a two week washout period for MAOIs prior to elective surgery and ECT on theoretical grounds. However, El-Ganzouri et al (1985) monitored the vitals (blood pressure, pulse and body temperature) of 13 patients receiving MAOIs who were administered 22 ECTs. The data were compared to a control group of patients not receiving MAOIs having ECTs with identical premedication and anesthesia. There were no significant differences between ECT-treated patients with or without MAOIs and no adverse clinical events occurred in either group. The authors concluded that they believed that "discontinuation of chronic MAOI therapy prior to surgery is not necessary." However, as noted below, there is a potential drug interaction between succinlylcholine and phenelzine that ought to be considered if the patient does remain on the MAOI during ECT. Additionally, if patients happen to experience a hypotensive episode, the use of any sympathomimetic agent may be problematic due to the risk of developing hypertensive crises with their combination. Therefore, the most conservative recommendation is to discontinue the MAOI for 10-14 days prior to starting ECT. However, if a patient receiving an MAOI requires immediate surgery this may not be possible.
MAOI-DRUG INTERACTIONS (Hansten and Horn 1992)
MAOIs inhibit many enzyme systems in the liver and body other than MAO. Thus, drugs that are metabolized by such enzymes have the activity either potentiated or inhibited by the MAOIs. Table 8 summarizes these drug interactions. The most notable include sympathomimetic amines, anorexiants, SSRIs, meperidine and dopamine precursors.
|
TABLE 1: PREVALENCE OF MAOI ADVERSE EFFECTS VS. IMIPRAMINE AND PLACEBO |
||||
|
Adverse Effect |
|
|
|
|
|
|
|
|
|
|
|
Hypomania |
|
|
|
|
|
Hypertensive Crises |
|
|
|
|
|
Convulsions |
|
|
|
|
|
Syncope |
|
|
|
|
|
Disorientation |
|
|
|
|
|
Edema* |
|
|
|
|
|
Rash* |
|
|
|
|
|
Weight Gain >15 lb* |
|
|
|
|
|
Urinary Retention |
|
|
|
|
|
Paresthesias |
|
|
|
|
|
Drowsy* |
|
|
|
|
|
Anorgasmia-impotence |
|
|
|
|
|
Other* |
|
|
|
|
|
None |
|
|
|
|
|
TABLE 2: ADVERSE EFFECTS INCIDENCE OF PHENELZINE 60 MG/D VERSUS AMITRIPTYLINE 150 MG/D FOR SIX WEEKS |
||
|
Adverse Effect |
|
|
|
Dry Mouth |
|
|
|
Sedation |
|
|
|
Faintness/Dizziness |
|
|
|
Constipation |
|
|
|
Headache |
|
|
|
Restlessness |
|
|
|
Edema |
|
|
|
Indigestion |
|
|
|
Difficult urination |
|
|
|
Nausea |
|
|
|
Number (x ± SD) |
|
|
|
TABLE 3: COMPARATIVE MAOI ADVERSE EFFECTS BASED ON SHEEHAN'S CLINICAL EXPERIENCE |
|||
|
ADVERSE EFFECT |
(PARNATE) |
(NARDIL) |
(MARPLAN) |
|
Hypertension |
|
|
|
|
Hepatotoxicity |
|
|
|
|
Orthostatic Hypotension |
|
|
|
|
CNS Stimulation |
|
|
|
|
Sedation |
|
|
|
|
Appetite Stimulation |
|
|
|
|
Muscle twitch |
|
|
|
|
Edema |
|
|
|
|
Sexual Dysfunction |
|
|
|
|
Urinary Retention |
|
|
|
|
TABLE 4: TYRAMINE-CONTAINING FOODS PRECIPITATING HYPERTENSIVE CRISIS |
||
|
|
|
|
|
|
|
|
|
Cheeses |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
TABLE 5: TYRAMINE-CONTAINING FOODS PRECIPITATING HYPERTENSIVE CRISIS |
||
|
|
|
|
|
Fish |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Meat |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Fruit |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Yeast Extracts |
|
|
|
|
|
|
|
|
|
|
|
Miscellaneous |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
TABLE 6: TYRAMINE CONTENT OF COMMON FOODS THAT CAN PRECIPITATE HYPERTENSIVE CRISIS WITH MAOIs DUE TO INGESTION OF 25 MG OF TYRAMINE |
||
|
Food |
|
(gm or ml) |
|
Cheddar cheese, old |
|
|
|
Beer |
|
(19-104 beers) |
|
Sherry Wine |
|
|
|
Chianti Wine |
|
|
|
TABLE 7: RELATIVE RESTRICTIONS OF FOODS AND BEVERAGES WITH MAOI USE (GARDNER ET AL 1996) |
|
|
Restriction |
Foods |
|
Absolute |
Aged cheeses, aged and cured meats, banana peel, broad bean pods, improperly stored or spoiled meats, poultry, and fish, Marmite, sauerkraut, soy sauce and other soybean condiments, tap beer |
|
Moderate |
Red or white wine, bottled or canned beer (including nonalcoholic varieties) |
|
Unnecessary |
Avocados, bananas, beef/chicken bouillon, chocolate, fresh and mild cheeses (e.g., ricotta, cottage, cream cheese, processed slices), fresh meat, poultry or fish, gravy (fresh), monosodium glutamate, peanuts, properly stored pickled or smoked fish (e.g. herring), raspberries, soy milk, yeast extracts (except Marmite) |
|
TABLE 8: MAOI-Drug Interactions (Hansten and Horn 1992) |
||
|
Drug |
Effect |
Mechanism |
|
Sympathomimetic Amines |
Hypertensive crisis |
MAOIs increased storage and sympathomimetics increase release of norepinephrine |
|
Anorexiants |
hypertensive crisis |
An increase in norepinephrine at synaptic cleft |
|
Dopamine precursors |
Hypertensive crisis |
Increase in storage and release of dopamine, norepinephrine or both |
|
Narcotic analgesics |
Excitation, sweating, hyperpyrexia, rigidity, hypertension to hypotension, seizures, coma, death |
Not established but thought to be a CNS serotonin toxicity syndrome due to meperidine blocking neuronal reuptake of serotonin; use morphine, oxycodone, codeine, or NSAIDs |
|
Antidepressants |
Hyperthermia, neuromuscular irritability, confusion |
Serotonin Syndrome - serotonin agonists such as cyprohepatidine (Periactin) and methysergide (Sansert) counteract the interaction in animals; less severe with phenelzine than tranylcypromine according to animal studies; wait 10 weeks to start MAOI and 2 weeks to start fluoxetine (Feighner et al 1990)
|
|
Barbiturates |
excessive sedation to point of being semi-comatose |
Inhibition of barbiturate metabolism |
|
Tricyclic Antidepressants |
Sympathetic hyperactivity, i.e., hyperpyrexia and hypertension |
not established; see above |
|
Antidiabetics |
Excessive hypoglycemia |
Hypothesized that MAOIs interfere with the compensatory adrenergic response to hypoglycemia; TCP stimulated insulin secretion by beta-adrenergic stimulation |
|
Reserpine |
Hypertensive Reaction |
Increased storage and release of norepinephrine |
|
Succinlycholine |
Prolonged muscle relaxation |
Phenelzine may decrease plasma pseudocholinesterase |
|
Buspirone |
transient hypertension with no sequelae (Gelenberg 1990) |
|
|
Carbamazepine |
no interaction based on a n of 1 (Joffe et al 1985) |
|
REFERENCES
Anonymous (1989). Foods interacting with MAO inhibitors. Medical Letter 13:11-12.
Bieck PR, Antonin KH (1988). Oral tyramine pressor test and the safety of monoamine oxidase inhibitor drugs: Comparison of brofaromine and tranylcypromine in healthy subjects. J Clin Psychopharmacol 8:237-45.
Bieck PR, Firksuny L, Schick C, et al (1989). MAO inhibition by phenelzine and brofaromine in healthy volunteers. Clin Pharmacol Ther 45:260-9.
Bethune HC, Burrell RH, Culpan RH, et al (1964). Vascular crisis associated with monoamine oxidase inhibitors. Am J Psychiatry 121:245-8.
Bowden CL, Seleshi E, Javors MA (1989). Mania associated with high percentage of inhibition of monoamine oxidase. Am J Psychiatry 146:121.
Clary C, Schweizer E (1987). Treatment of MAOI hypertensive crisis with sublingual nifedipine. J Clin Psychiatry 48:249-50.
DeCastro R (1985). Reversal of MAOI-induced anorgasmia with cyproheptadine. Am J Psychiatry 142:783.
El-Ganzouri AR, Ivankovich AD, Braverman B, et al (1985). Monoamine oxidase inhibitors: should they be discontinued preoperatively? Anesth Analog 64:592-6.
Feighner JP, Boyer WF, Tyler DL, et al (1990). Fluoxetine and MAOIs: Adverse interaction. J Clin Psychiatry 51:222-5.
Gardner DM, Shulman KI, Walker SE, et al (1996). The making of a user friendly MAOI diet. J Clin Psychiatry 57:99-104.
Gelenberg AJ (1984). Switching MAOIs. Biol Therap Psychiatry 7:37.
Gelenberg AJ (1988). MAOIs: assorted concerns. Biol Therap Psychiatry 11:33-6.
Gelenberg AJ (1990). Buspirone-MAOI Interaction. Biol Therap Psychiatry 13:36.
Golwyn DH, Sevlie CP (1993). Monoamine oxidase inhibitor hypertensive crisis headache and orthostatic hypotension [letter]. J Clin Psychopharmacol 13:77-8.
Graham PM, Potter JM, Paterson JW (1982). Combination monoamine oxidase inhibitor / TCA interaction. (letter). Lancet 2:440.
Grossman E, Messerli FH, Grodzicki T, et al (1996). Should a moratorium be placed on sublingual nifedipine capsules given for hypertensive emergencies and pseudoemergencies? JAMA 276:1328-31.
Hansten PD, Horn JR (1992). Drug Interactions. Vancouver, WA, Applied Therapeutics.
Horowitz D, Lovenberg W, Engelmann K, et al (1964). Monoamine oxidase inhibitors, tyramine, and cheese. JAMA 188:1108.
Joffe RT, Post RM, Uhde TW (1985). Lack of pharmacokinetic interaction of carbamazepine with tranylcypromine (letter). Arch Gen Psychiatry 42:738.
Joyce PR, Walshe J (1983). Nightmares during phenelzine withdrawal. J Clin Psychopharmacol 3:121.
Keck PE Jr, Vuckovic A, Pope HG Jr, et al (1989). Acute cardiovascular response to monoamine oxidase inhibitors: a prospective assessment. J Clin Psychopharmacol 9:203-6.
Kronig MH, Roose SP, Walsh BT, et al (1983). Blood pressure effects of phenelzine. J Clin Psychopharmacol 3:307-10.
Lieberman JA, Kane JM, Reife R (1986). Neuromuscular effects of monoamine oxidase inhibitors. Adv Neurol 43:231-49.
Liskin B, Roose SP, Walsh BT, et al (1985). Acute psychosis following phenelzine discontinuation. J Clin Psychopharmacol 5:46-7.
Loveless AH, Maxwell HR (1965). A comparison of the effects of imipramine, trimipramine, and some other drugs in rabbits treated with a monoamine oxidase inhibitor. Br J Pharmacol 25:158-70.
McGrath PJ, Stewart JW, Quitkin FM (1989). A possible L-deprenyl induced hypertensive reaction (letter). J Clin Psychopharmacol 9:310-1.
Nierenberg AA, Keck PE Jr (1989). Management of MAOI-associated insomnia. J Clin Psychopharmacol 4:42-5.
Palladino A (1983). Adverse reactions to abrupt discontinuation of phenelzine. J Clin Psychopharmacol 3:206-7.
Ponto LB, Perry PJ, Liskow BI, et al (1977). Tricyclic antidepressant and monoamine oxidase inhibitor combination therapy. Am J Hosp Pharm 6:954-61.
Rabkin J, Quitkin F, Harrison W, et al (1984). Adverse reactions to monoamine oxidase inhibitors. Part I. A comparative study. J Clin Psychopharmacol 4:270-8.
Rabkin JG, Quitkin FM, McGrath P, et al (1985). Adverse reactions to monoamine oxidase inhibitors. Part II. Treatment correlates and clinical manage-ment. J Clin Psychopharmacol 5:2-9.
Raisfeld IH (1972). Cardiovascular complications of antidepressant therapy. Am Heart J 83:129-33.
Risch SC, Groom GP, Janowsky DS (1982). The effects of psychotropic drugs on the cardiovascular system. J Clin Psychiatry 43:16-31.
Robinson DS, Nies A, Corcella J, et al (1982). Cardiovascular effects of phenelzine and amitriptyline in depressed outpatients. J Clin Psychiatry 43:8-15.
Segraves RT (1987). Reversal by bethanecol of imipramine-induced ejaculatory dysfunction (letter). Am J Psychiatry 144:1243-4.
Sheehan DV, Claycomb JB, Kouretas N (1980-1). Monoamine oxidase inhibitors. Pre-scription and patient management. Int J Psychiatry Med 10:99-109.
Shulman KI, Walker SE, MacKenzie S, et al (1989). Dietary restriction, tyramine, and the use of monoamine oxidase inhibitors. J Clin Psychopharmacol 9:397-402.
Sjoqvist F (1965). Psychotropic drugs (2). Interaction between monoamine oxi-dase (MAO) inhibitors and other substances. Proc Roy Soc Med 58(suppl):967-78.
Stewart JW, Harrison W, Quitkin F, et al (1984). Phenelzine-induced pyridoxine deficiency. J Clin Psychopharmacol 4:225-6.
Stewart MM (1976). MAOI and food--fact and fiction. Adverse Drug Reaction Bulletin 58:200-3.
Teicher MH, Cohen BM, Baldessarini RJ, et al (1988). Severe daytime somnolence in patients treated with an MAOI. Am J Psychiatry 145:1452-6
True BL, Alexander B, Carter B (1985). Switching monoamine oxidase inhibitors. Drug Intell Clin Pharm 19:825-7.
Walker SE, Shulman KI, Tailor SA, et al (1996). Tyramine content of previously restricted foods in monoamine oxidase inhibitor diets. J Clin Psychopharmacol 16:383-8.
Zimmerman HJ, Ishak KG (1987). The hepatic injury of monoamine oxidase inhibitors. J Clin Psychopharmacol 7:211-3.