MONOAMINE OXIDASE INHIBITOR ANTIDEPRESSANTS
Monoamine oxidase inhibitors produce their antidepressant action as the result of increasing brain concentrations of monoamine neurotransmitter substances by blocking monoamine oxidase-catalyzed metabolic degradation of these substances. Since both reuptake mechanisms and metabolic inactivation of neurotransmitters may increase their availability and activity within the brain, these two antidepressant mechanisms are theoretically complementary. It is theoretically possible that combined tricyclic MAOI therapy could provoke a higher incidence of hypertensive reactions. Based on controlled studies and clinical observation, this drug combination does not appear to be associated with a high risk of hypertensive crises. The most commonly encountered unwanted effect of MAOI antidepressants is the production of postural hypotension, which may, in fact, be enhanced in some patients receiving tricyclics in combination with MAOls. When combined therapy regimens are utilized, patients should be carefully monitored before and during treatment, and it is preferable that the patient previously receive both types of antidepressant singly so that the adverse effects of the individual drug may be seen before the patient is exposed to combination therapy.
Tranylcypromine is a nonhydrazine, while phenelzine and isocarboxazid are both hydrazine compounds. The hydrazine structure may be potentially hepatoxic, though the incidence of reported liver damage with these drugs is exceedingly low. Tranylcypromine structurally resembles the amphetamines and may produce some direct stimulant action in addition to the pharmacologic effects resulting from enzyme inhibition. Although hypertensive reactions to tranylcypromine in the absence of food or drug interactions have been suggested, there is no convincing evidence that they do in fact occur. A patient who has been treated with phenelzine and subsequently abruptly started on tranylcypromine may experience a potentially fatal hypertensive reaction. Therefore in changing treatment from another MAOI to tranylcypromine, a five- to ten-day drug-free interval is advised; when changing from tranylcypromine to another MAOI a drug-free interval is not required.
The most widely known drug interaction in psychiatry is the hypertensive reaction that may occur when tyramine-rich foods or beverages are consumed by a patient being treated with an MAOI. See appendix A and chapter 6 for a full discussion.
Patients being treated with MAOls should generally limit their daily intake of caffeine-containing beverages, including coffee, tea, and cola drinks to three cups or glasses per day. If a patient tends to consume large quantities of these beverages, he or she should be advised to drink decaffeinated products. White wine is generally less likely to contain significant quantities of tyramine than is red wine, Chianti being particularly high in its tyramine content. Many beers are also rich in tyramine. Fermented liquors generally do not contain significant quantities of tyramine, but since MAOls tend to potentiate alcohol, the effects of these beverages may be enhanced by drug therapy. A single cocktail or 3 oz of white wine can be safely consumed. Small quantities of sour cream, yogurt, cottage cheese, American cheese, or chocolate may be consumed during the course of MAOI therapy, generally without ill effect.
Patients receiving MAOI antidepressants should be told specifically to avoid the use of nose drops, cold remedies, nasal decongestants, cough syrups, diet pills, and any other prescription or over-the-counter remedy that may contain vasoconstrictor or stimulant-type drugs. The current epidemic of cocaine abuse indicates the necessity to specifically warn patients against the use of cocaine while taking an MAOI. The author has seen two patients who have experienced this unfortunate drug interaction, which was manifested clinically by moderate hypertension and a pronounced but relatively transient acute psychosis. One of the patients experienced this reaction on several occasions despite strong warnings to avoid cocaine use. Patients suffering from bronchial asthma who may be medicated with ephedrine, epinephrine, or other bronchodilators have a rather high risk of experiencing a drug-drug interaction during the course of MAOI antidepressant therapy. Therefore, generally, asthmatic patients should not receive this form of antidepressant treatment unless their asthma can be adequately controlled by the intermittent use of steroid inhalers such as beclomethasone. Meperidine may produce hypertension, hyperpyrexia, and death when administered to MAOI -treated patients.
Patients who develop hypertensive reactions as a result of the combination of vasoactive substances with MAOI antidepressants frequently respond adequately to mild sedation administered in a quiet, darkened room. More severe hypertensive reactions generally are best treated by the IV administration of phentolamine (Regitine) in a dose of 5 mg. Propranolol, a B-adrenergic blocking agent administered slowly IV alone or in combination with the alpha-adrenergic blocking drug phentolamine, may also be useful in the presence of a severe hypertensive crisis. Sublingual nifedipine may also be useful in managing MAOI hypertensive crises.
Pargyline hydrochloride (Eutonyl), an MAOI, has been used for a number of years as an antihypertensive drug. This compound also exerts an antidepressant effect and may be very useful in the treatment of depressed hypertensive patients. There are a number of potential drug interactions between MAOIs and antihypertensive medications. Guanethidine when initially administered causes the release of norepinephrine from nerve endings. An MAOI -treated patient who is started on guanethidine or clonidine may experience a hypertensive reaction followed by severe hypotension. Hydralazine is likely to produce more pronounced tachycardia and possibly an elevation in blood pressure in an MAOI -treated patient. Methyldopa can also provoke a hypertensive reaction in a patient receiving MAOI antidepressants.
The most common unwanted effect of MAOI antidepressants is a decrease in blood pressure, most prominent with postural change from a reclining or sitting position to a standing position. Any vasodilator is likely to enhance the hypotensive reaction. Phenothiazines, particularly low-potency agents such as chlorpromazine and thioridazine, are particularly likely to provoke significant hypotensive reactions when given to patients receiving MAOIs. If a neuroleptic is necessary in conjunction with this form of antidepressant drug therapy, piperazine phenothiazines such as trifluoperazine or the butyrophenone haloperidol, are clearly the safest drugs with the least likelihood of producing a hypotensive reaction. Levodopa, a common antiparkinsonian medication, may provoke pronounced CNS stimulation and hypertension in conjunction with MAOIs. A similar reaction may occur with the respiratory center stimulant doxapram.
Central nervous system depressants including alcohol, barbiturates, benzodiazepines, chloralhydrate, and opiates are generally potentiated by MAOIs, so that excessive sedation and CNS depression results.
The narcotic analgesic meperidine, when administered to an MAOI treated patient, may provoke a serious and fatal adverse reaction. The MAOI – meperidine reaction is characterized by agitation, restlessness, headache, rigidity, and hyperpyrexia. It may be associated with profound hypotension or dramatic hypertension, convulsions may occur, the patient may become comatose and, indeed, deaths have been reported from this syndrome. The administration of meperidine to MAOI-treated patients is absolutely contraindicated.
Although emergency surgery under general anesthesia can be safely accomplished during the course of MAOI therapy, it is generally preferable to delay elective surgical procedures for 1 to 2 weeks after discontinuing these drugs. In addition to the risk of a drug interaction involving the administration of pressor agents to an MAOI-treated patient during the course of surgery, several drug interactions involving anesthetics have been reported. Halothane and enflurane have both been observed to produce muscle stiffness and hyperpyrexia in MAOI-treated patients. Succinylcholine and related muscle relaxants may have their paralytic effect enhanced and prolonged as the result of MAO inhibition. Furthermore, as stated previously, barbiturates, including those used for general anesthesia may be potentiated by this form of antidepresssant drug therapy. Table 12-4 delineates the spectrum of drug interactions involving MAOIs.