Monoamine Oxidase Inhibitors (MAOIs) - Antidepressants for Major Depression

Monoamine oxidase inhibitors (MAOIs) are one of the oldest classes of antidepressants and are typically used when other antidepressants have not been effective. They are used less frequently because they often interact with certain foods and require strict dietary restrictions. MAOIs can also result in severe adverse reactions if taken with many other medicines, including some over-the-counter cough and cold remedies. MAOIs are mostly used for atypical depression.

A newer type of MAOI called moclobemide is slightly different to the older MAOIs. It is considered to be a safer choice than the older MAOIs, as it requires fewer dietary restrictions and has fewer significant interactions with other medicines. Moclobemide is considered a second-line treatment for major depression.

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How do MAOIs work?
It is thought that depression may be linked to an imbalance of chemicals within the brain.
Within the brain there are chemical messengers or neurotransmitters, called monoamines. Examples of these are noradrenaline and serotonin.

Neurotransmitters are involved in controlling or regulating bodily functions, and noradrenaline and serotonin are involved in the control and regulation of mood.
When depression occurs, there may be a decrease in the amount of these monoamines released from nerve cells in the brain. Monoamines are broken down by a chemical (enzyme), called monoamine oxidase.

MAOIs prevent monoamine oxidase from breaking down the monoamines. This results in an increased amount of active monoamines in the brain.

By increasing the amount of monoamines in the brain, the imbalance of chemicals, thought to be important in causing depression, is altered. This helps relieve the symptoms of depression.

Moclobemide is a more selective type of MAOI, called a reversible inhibitor of monoamine oxidase type A (RIMA). It works specifically on monoamine oxidase type A, which gives it its slightly different profile.

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How long do MAOIs take to work?
MAOIs can take a while to have an effect so you may not feel better immediately when you start treatment with one.

You may experience an effect on your mood within two weeks, however, the full benefits of treatment with MAOIs may not occur for a further two to four weeks. It is important to keep taking the medicine even if you think it is not working at first.

If you feel your depression has got worse, or if you have any distressing thoughts or feelings in these first few weeks, then you should talk to your doctor.

How long will I have to take them for?
MAOIs usually help mood improve over a number of weeks or months. Even when things seem back to normal, you should keep taking them for a further six months to minimise the chances of the depression coming back.

Are they addictive?
No. It is possible for MAOIs to produce unpleasant withdrawal symptoms (sometimes called a discontinuation syndrome) when they are stopped. But this is temporary, does not involve a craving for the medication, and can usually be avoided if the drug is tapered off rather than stopped suddenly. This is not addiction.

Withdrawal symptoms may include nausea, headache, insomnia, giddiness, vivid dreams, agitation and irritability. These can sometimes occur if you miss a dose of the antidepressant, which is why it is important to take them as directed by your doctor.
When stopping treatment withdrawal symptoms can be minimized or avoided if the dose of the MAOI is gradually decreased over a period of a few weeks. Your doctor will help you do this.

Some people develop a tolerance to MAO inhibitors. This could mean that the drug will work for you at first, but you could suddenly become depressed again in the middle of treatment. This sort of reaction is particularly disturbing because it sets off a plummeting depression that may not respond to any other antidepressant. Oddly, if you develop tolerance to an MAOI, the best solution may be to switch to another antidepressant for a few weeks, and then start taking the same MAOI again. This way, the drug may regain its effectiveness.

The MAO inhibitors are somewhat more dangerous drugs than other antidepressants when taken in excessive amounts -- far more so than newer drugs such as Prozac, Zoloft or Desyrel. Symptoms of overdose include severe anxiety, confusion, convulsions or seizures, cool clammy skin, severe dizziness, severe drowsiness, fast and irregular pulse, fever, hallucinations, severe headache, high or low blood pressure, muscle stiffness, breathing problems, severe sleeping problems, or unusual irritability.

Side Effects
Unfortunately, monoamine oxidase doesn't just destroy neurotransmitters to increase level of monoamines in the brain; it's also responsible for mopping up another amine called tyramine, a molecule that affects blood pressure. So when monoamine oxidase gets blocked, levels of tyramine begin to rise, too. And that's when the trouble starts.

While a hike in neurotransmitters is beneficial, an increase in tyramine is disastrous. Excess tyramine can cause a sudden, sometimes fatal increase in blood pressure so severe that it can burst blood vessels in the brain.

Every time you eat chicken liver, aged cheese, broad-bean pods, or pickled herring, tyramine floods into your brain. Normally, MAO enzymes take care of this potentially harmful tyramine excess. But if you're taking an MAO inhibitor, the MAO enzyme can't stop tyramine from building up. This is exactly what happened when the drugs were introduced in the 1960s. Because no one knew about the tyramine connection, a wave of deaths from brain hemorrhages swept the country. Other patients taking MAO inhibitors experienced severe headaches caused by the rise in blood pressure. These early side effects were particularly disturbing because nobody knew why they were happening.

The mystery was solved when a British pharmacist noticed that his wife, who was taking MAO inhibitors, got headaches when she ate cheese. But the early MAOIs were considered so dangerous (they also can damage the liver, brain, and cardiovascular systems) that even after the MAO-tyramine connection was finally understood, these drugs were taken off the American market for a time. (A related European antidepressant drug, Deprenyl, is marketed in this country as an anti-Parkinson's medication; it requires less stringent dietary cautions.)

Eventually the MAOIs were reintroduced in this country despite the tyramine risk because some depressed people don't respond to any other medication. Nevertheless, MAO inhibitors are usually the antidepressant of last resort.

"I call it the 'St. Jude' drug," says psychiatrist Andy Myerson. "It's the drug I use when nothing else works and someone is willing to give up anything in the hope that something will help their depression."

Side effects of MAOIs include:
  • Drowsiness
  • Constipation
  • Nausea
  • Diarrhea
  • Stomach upset
  • Fatigue
  • Dry mouth
  • Dizziness
  • Low blood pressure
  • Lightheadedness, especially when getting up from a lying or sitting position
  • Decreased urine output
  • Decreased sexual function
  • Sleep disturbances
  • Muscle twitching
  • Weight gain
  • Blurred vision
  • Headache
  • Increased appetite
  • Restlessness
  • Shakiness
  • Trembling
  • Weakness
  • Increased sweating

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Safety concerns with MAOIs
MAOIs can cause dangerous interactions with certain foods and beverages. And you can understand why. If you take MAOIs, you'll face dietary restrictions that require you to limit consumption of foods that contain a high level of tyramine, such as many cheeses, pickled foods, chocolates, certain meats, beer, wine, and alcohol-free or reduced-alcohol beer and wine. The interaction of tyramine with MAOIs can cause a dangerously high increase in blood pressure, which can lead to a stroke. Your doctor can give you a complete list of dietary restrictions.

Emsam may offer a way to avoid these dietary restrictions. At its lowest dose of 6 milligrams a day, you don't need to follow those dietary restrictions. At higher doses of Emsam, you do, though. Talk to your doctor or mental health provider to see if this may be an option for you.

MAOIs can also cause serious reactions when you take them while you're also taking certain other medications. Examples of medications to avoid include other antidepressants, certain pain medications such as tramadol (Ultram) and meperidine (Demerol) over-the-counter decongestants and herbal weight-loss products, and St. John's wort. Always check with your doctor or pharmacist before taking any new prescription medication, over-the-counter medication or supplement while taking MAOIs.

Dietary Restrictions
Don't eat or drink any of the following when taking MAOIs unless your doctor advises otherwise:
  • aged foods
  • alcoholic beverages (especially chianti, sherry, liqueurs, and beer)
  • alcohol-free or reduced-alcohol beer or wine
  • anchovies
  • bologna, pepperoni, salami, summer sausage, or any fermented sausage
  • caviar
  • cheeses (especially strong or aged varieties), except for cottage and cream cheese
  • chicken livers
  • fermented foods
  • figs (canned)
  • fruit: raisins, bananas (or any overripe fruit)
  • meat prepared with tenderizers; unfresh meat; meat extracts
  • smoked or pickled meat, poultry, or fish
  • soy sauce
Foods you can eat in moderation:
  • avocados
  • beer
  • caffeine (including chocolate, coffee, tea, cola)
  • chocolate
  • raspberries
  • sauerkraut
  • soup (canned or powdered)
  • sour cream
  • yogurt

Serotonin syndrome and MAOIs
A rare but potentially life-threatening side effect of MAOIs is serotonin syndrome. This condition, characterized by dangerously high levels of serotonin in the brain, can occur when an MAOI interacts with another type of antidepressant called selective serotonin reuptake inhibitors (SSRIs). Because of this, don't take any MAOIs while you're taking any SSRIs or within two weeks of each other. Serotonin syndrome requires immediate medical treatment.

Signs and symptoms of serotonin syndrome include:
  • Confusion
  • Restlessness
  • Hallucinations
  • Extreme agitation
  • Fluctuations in blood pressure
  • Increased heart rate
  • Nausea and vomiting
  • Fever
  • Seizures
  • Coma
Stopping treatment with MAOIs
Discontinuation of MAOIs has been associated with nausea, vomiting and malaise. Rarely, discontinuation has caused an uncommon withdrawal syndrome involving vivid nightmares with agitation, psychosis and convulsions. The syndrome is treated with a low-dose MAOI and more gradual tapering off. Talk to your doctor before stopping treatment with MAOIs.

Suicidal feelings and MAOIs
In some cases, antidepressants may be associated with worsening symptoms of depression or suicidal thoughts or behavior in those ages 18 to 24. It's likely to occur in the first one to two months of treatment or when you change your dosage. Be sure to talk to your doctor about any changes in your symptoms. You may need more careful monitoring when beginning or changing treatment, or you may need to stop the medication if your symptoms worsen. Adults age 65 and older taking antidepressants have a decreased risk of suicidal thoughts.

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Several Types of MAO Inhibitors and Their Dosages
-        Isocarboxazid (Marplan)
Usual Starting Dose: 30 mg/day
Maximum Dose: 30 mg/day
-        Phenelzine (Nardil)
Usual Starting Dose: 15 mg/day
Maximum Dose: 60 mg/day
-        Tranylcypromine (Parnate)
Usual Starting Dose: 30 mg/day
Maximum Dose: 60 mg/day

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