A reversible monoamine oxidase inhibitor, or RIMA, is a type of antidepressant from the monoamine oxidase inhibitor (MAOI) class, which were the first antidepressants developed. What sets RIMAs apart is their temporary mode of action, a defining feature that distinguishes them from older MAOIs and influences their safety profile and medical use.
How Reversible MAOIs Work
To understand how these medications function, one must first consider monoamine oxidase (MAO) enzymes. In the brain, MAO enzymes break down chemical messengers called neurotransmitters, clearing them from the space between nerve cells. The MAO-A isoenzyme specifically metabolizes mood-regulating neurotransmitters like serotonin, norepinephrine, and dopamine.
Reversible MAOIs work by temporarily binding to the MAO-A enzyme, which prevents it from metabolizing these neurotransmitters. This blockage increases the availability of serotonin, norepinephrine, and dopamine in the brain, which is believed to help alleviate symptoms of depression.
This temporary connection means the medication can be displaced from the enzyme, allowing it to resume its function quickly. This differs from older, irreversible MAOIs, which form a permanent bond that deactivates the enzyme. The body must then synthesize new enzymes to restore function, a process that can take weeks. The temporary nature of reversible MAOIs allows for a more flexible pharmacological effect.
Key Differences from Traditional MAOIs
A primary distinction between reversible and traditional, irreversible MAOIs is the risk of a food interaction. Older, irreversible MAOIs can cause a hypertensive crisis, a sudden and severe spike in blood pressure, when combined with certain foods. This reaction, known as the “cheese effect,” is caused by an amino acid called tyramine.
Tyramine is found in aged, fermented, or cured foods like strong cheeses and cured meats. The MAO-A enzyme in the gut and liver normally breaks down tyramine. Irreversible MAOIs block this enzyme, allowing tyramine to enter the bloodstream and trigger a massive release of norepinephrine, which can dangerously increase blood pressure.
Reversible MAOIs present a much lower risk of this reaction. Because the inhibitor binds reversibly, high concentrations of tyramine can displace the medication from the MAO-A enzyme. This allows the enzyme to become active again and metabolize the excess tyramine, preventing its buildup. Due to this safety advantage, strict dietary restrictions are often not required with RIMAs at standard doses.
Another difference is the shorter “washout period” needed when switching to another antidepressant. Since irreversible MAOIs permanently disable the enzyme, a two-to-three-week period is necessary for the body to create new enzymes. The faster dissociation of reversible MAOIs means this washout period is considerably shorter, offering more flexibility in treatment.
Medical Uses and Applications
Reversible MAOIs are prescribed for Major Depressive Disorder (MDD) and have shown efficacy similar to other antidepressants like tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). They are also considered for patients with atypical depression, a subtype characterized by mood reactivity, increased appetite, and excessive sleepiness.
Reversible MAOIs are also an effective treatment for social anxiety disorder, also known as social phobia. Clinical trials have demonstrated their effectiveness in reducing symptoms, although benefits may take several weeks to become apparent.
The most widely known example of a reversible MAOI is moclobemide, available in countries like Canada, the United Kingdom, and Australia. Due to its favorable side effect profile, moclobemide is sometimes recommended for depression in elderly patients, as it is well-tolerated and may improve associated cognitive impairments.
Potential Side Effects and Drug Interactions
Reversible MAOIs have potential side effects, though they are often better tolerated than older antidepressants. Common side effects can include insomnia, dizziness, and nausea. These effects are often mild, may diminish as the body adjusts, and taking the medication after a meal can sometimes help.
A more significant concern is the risk of drug interactions, the most serious being serotonin syndrome. This is a potentially life-threatening condition caused by excessive serotonin activity in the brain. It occurs when a reversible MAOI is combined with other drugs that increase serotonin levels, with symptoms ranging from agitation and confusion to rapid heart rate and muscle rigidity.
To prevent serotonin syndrome, reversible MAOIs must not be taken with other serotonergic drugs. Caution is required with several types of substances:
- Prescription antidepressants like SSRIs, SNRIs, and tricyclics
- Triptan medications used for migraines
- Over-the-counter cold medicines containing dextromethorphan
- Illicit drugs such as MDMA (ecstasy)
Patients should inform their healthcare provider of all medications and supplements they are taking.