Monoamine oxidase inhibitors (MAOIs) were among the first antidepressants to be discovered. They work by slowing down the action of monoamine oxidase, an enzyme that helps dismantle chemical messengers (neurotransmitters, including serotonin, norepinephrine and dopamine). By stalling their breakdown, MAOIs increase the availability of these chemical messengers, modifying nerve pathways that control mood. MAOIs are as effective as any other antidepressant, but you must avoid certain foods and drugs (see below). Because of this inconvenience, MAOIs are prescribed relatively infrequently.

One reason MAOIs are still used is that they work differently from other antidepressants, so they may work when other drugs have not. MAOIs are also effective for treating panic and other anxiety disorders.

MAOIs may be taken two or three times per day, with or without food. Older adults generally take lower doses.

MAOIs are associated with the following side effects. Always report any new symptoms to your doctor, whether they are on this list or not:

While taking MAOIs, you must follow a strict diet. The enzyme blocked by MAOIs also helps to break down tyramine, a substance found in some foods. High levels of tyramine can cause a quick and dangerous rise in blood pressure. So, if you take MAOIs, you must avoid foods with tyramine. Some aged, ripened or fermented foods have too much tyramine in them, including:

Some drugs can interact with MAOIs and should be avoided completely. Other drugs can be taken under the close supervision of your doctor.

Tell your doctor about any drugs you are taking, especially:

Cocaine can be deadly on its own. When combined with MAOIs, it can cause dangerously high blood pressure.

Suicide Risk. All antidepressants carry warnings about suicide. In October 2004, the Food and Drug Administration began requiring that manufacturers include a warning on package inserts for all antidepressants. The warning mentions the risk of suicidal thoughts, hostility and agitation in both children and adults.

After you start taking any antidepressant, there is a risk that you may feel worse rather than better. The danger is greatest in the first few weeks of treatment, so make sure you follow-up with your doctor. There is also a small risk for an increase in suicidal thinking and behavior. Fortunately, some research shows that the overall suicide rate decreases in people taking antidepressants. However, a small number of people using antidepressants do encounter a lower mood, and feel more anxious, irritable, self-destructive or impulsive.

Stopping your MAOIs. Because MAOIs have a stimulant effect, you may become depressed, anxious, agitated, sleepless or drowsy when you stop taking them, just as you would as if you stopped taking a stimulant drug. In addition, you may develop psychosis, which is distorted thinking such as hallucinations (false perceptions) or delusions (false ideas). This problem can usually be avoided if you decrease your dose slowly before stopping it.