Section III: A Very Brief History of the Different Families of Antidepressant Medications

Monoamine oxidase is a ubiquitous enzyme and within the nervous system appears to mediate the breakdown of both norepinephrine and serotonin. This is significant, as these are the two main neurotransmitters that we will discuss in understanding the use of antidepressant medications.

An inhibitor of this enzyme, or MAO inhibitor, is effective by reducing the breakdown of these neurotransmitters. This causes norepinephrine and serotonin to remain active for a longer time within the brain, particularly in the limbic region, where emotions and mood reside.

With more of these neurotransmitters available, mood is enhanced in complicated ways, thereby causing an antidepressant effect. With the introduction of the first MAO inhibitor in 1951, for the first time physicians had the capacity to combat problems with mood and affect with a medication.

There are two MAO inhibitors that we will briefly cover. They are Nardil (phenelozine) and Parnate (tranylcypromine). For the benefit of the trainee, we will present the important information on these medications on the following summary pages that can be printed and used for reference.

                                        Nardil Summary Page

Trade Name: Nardil (1960s) ........................Chemical Name: phenelozine
Antidepressant type: MAO Inhibitor......... Usual Dosage: 15-90 mg/qd
Pill sizes and types: Orange, biconvex glossy tablet of 15 mg.
How it Works: Inhibits the activity of the enzyme Monoamine Oxidase, which mediates the break down of serotonin and norepinephrine. This allows more of these neurotransmitters to act in the synaptic clefts between neurons of the limbic system.
Most Common Uses: Clients with atypical, non-endogenous depression, particularly with anxiety or phobia.
When Nardil is used as opposed to other medications: When other, more commonly used medications have failed to produce a therapeutic response.
Side-effects: The most serious side-effects involve increases and decreases in blood pressure, including possible hypertensive crisis. Other side-effects include insomnia, edema, weight gain, sexual dysfunction in terms of ejaculation and reaching orgasm, indigestion. Rarely, side-effects include manic reaction, convulsions, and ataxia.
Contraindications and cautions in use: Not to be taken by clients with congestive heart failure, history of liver disease, or a condition called pheocromocytoma. Not to be taken with other MAO medications. Must not be prescribed with antidepressants or other medications that elevate norepinephrine levels. Must not be added to medication regimen until other contraindicated medications have cleared metabolically, and other contraindicated medications should not be added until this has cleared system. Must not be taken in combination with buspirone or dexromethorphan. Patients on all MAO medications, including Nardil, must avoid foods high in tyramine - such as beer, chocolate, or aged cheese. Must also be administered carefully to hypertensive clients, and to clients with epilepsy. Nardil is not recommended for children under 16. It has not been established whether it is safe to take this medication during pregnancy or while breast feeding.
Comments: Due to the availability of medications with fewer dangers and side-effects, there are very limited circumstances under which this medication will currently be used. However, it is still used for clients who do respond to more common medications for depression.

                                       Parnate Summary Page

Trade Name: Parnate (1960s)................Chemical Name: tranylcypromine
Antidepressant type: MAO Inhibitor......... Usual Dosage: 30-60 mg/qd
Pill sizes and types: Orange, biconvex glossy tablet of 15 mg.
How it Works: Inhibits the activity of the enzyme Monoamine Oxidase, which mediates the break down of serotonin and norepinephrine. This allows more of these neurotransmitters to stay in action in the limbic system.
Most Common Uses: Moderate to severe depression, particularly with panic disorder. May also be used in psychotic depressive states, depressive states of bi-polar disorder.
When Parnate is used as opposed to other medications: In the treatment of severe endogenous depression, some patients respond to Parnate in lieu of electroconvulsive treatment (ECT), and when other antidepressants are not effective.
Side-effects: Hypomania, weight gain, sexual dysfunction in terms of ejaculation and reaching orgasm, increase or decrease in blood pressure, including possible hypertensive crisis, skin rash, blurred vision, occasional withdrawal effects, including nightmares, convulsions, agitation.
Contraindications and cautions in use: Not to be taken by clients with cardiovascular disorders, cerebrovascular disorders, liver damage, or history of headaches. Not to be taken with other MAO medications. Must not be prescribed with antidepressants or other medications that elevate norepinephrine levels. Must not be taken in combination with CNS depressants such as alcohol or depressant narcotics. Must not be added to medication regimen until other contraindicated medications have cleared metabolically, and other contraindicated medications should not be added until this has cleared system. Must not be taken in combination with reserpine, buspirone HCl or dexromethorphan. Clients should not receive cocaine based analgesics (lidocaine, Novocain) while on this medication. Patients on all MAO medications, including Parnate, must avoid foods high in tyramine - such as beer, chocolate, or aged cheese.
Comments: Due to the availability of medications with fewer dangers and side-effects, there are very limited circumstances under which this medication will currently be used.

What is important to know about these two medications? First, these medications are currently not used very frequently. Second, there are circumstances in which they are still useful. Third, when they are used, they must be used with careful planning and knowledge.

This is because this category of medications has many complications attached to their use. There are many uncomfortable and sometimes dangerous side-effects with these drugs. There are also many contraindications of use, and not just with other medications.

As some readers will know, the use of such medications must be accompanied with rigid dietary restrictions that include the limitation of aged cheeses, red wines, certain beans and beer. This is because these foods are rich in tyramine which also causes the release of norepinephrine.

The concomitant tyramine mediated release of norepinephrine, when occurring in conjunction with the use of MAO inhibitors, causes what is known as a hypertensive crisis. This is because the foods increase the amount of norepinephrine in the body, and the MAO inhibitors keep it active in the brain.

These events are extremely dangerous and can cause strokes. This is just one of the reasons why these medications were replaced when better options came along.

This type of reaction can occur not only with the foods described but also when using other antidepressant medications, both those that cause the increase of available norepinephrine, such as the tricyclic antidepressants, as well as the medications that cause an increase in available serotonin, such as the serotonin reuptake inhibitors.

Despite the dangers associated with this group of antidepressants and the availability of superior agents, some clinicians continue to find uses for these medicines. In fact the MAO inhibitors may be of value in certain atypical depressions, especially those which are associated with panic attacks, weight gain and hypersomnia.

However, even those atypical depressions are usually much more effectively treated with serotonin reuptake inhibitors (SSRIs) or other antidepressants, and I will discuss this later.

Typically, these medications will be the choice of last resort for clients who have not responded well to the later generations of antidepressants.

Because there is no absolute way to know in advance how real people are going to respond to the medicines, psychiatrists will usually begin by assessing what will be the most likely medication to be effective while also presenting the fewest side-effects.

When all of the less problematic options have been tried, and the client is still not responding, good psychiatrists will often consider using these MAO inhibitors.

As the reader can see from the summary pages, the choice to use them requires a great deal of evaluation and care, as there are many contraindications and uncomfortable and/or potentially dangerous side-effects that must be taken into account.

Since these medications are still in use, it is important to understand that they should not be used in combination with other antidepressants and that care must be taken to make sure that patients have been cleared of the other medications metabolically before adding these, and conversely these should be cleared from the patient before adding a subsequent antidepressant.

Dosages of Nardil tend to range from 15 mg. to 90 mg. and Parnate from 10 mg. to 30 mg.

Some of the more common side-effects of these medications include such things as orthostatic hypertension and indigestion, as well as sexual disturbances with respect to ejaculation and reaching orgasm.

There are more serious side-effects, too, including agitation and manic symptoms in some patients. In very rare cases, Nardil has been responsible for the precipitation of psychotic and acute anxiety reactions. Any mental health clinician with a client taking these medications should be sure that adequate medical care and supervision are being administered by a psychiatrist.



Review Questions for Section IV

At this point in the training, you should be able to answer the following questions:

1. What is the primary danger associated with the use of MAO medications?
2. What kinds of food must be avoided by patients taking MAO medications?
3. Under what conditions would the MAO medications be considered by a physician?

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