Monoamine Oxidase Inhibitors (MAOIs)

• Monoamine oxidase inhibitors (MAOIs) inhibit monoamine oxidase enzymes.
• MAO enzymes break down monoamine neurotransmitters in the brain such as serotonin, norepinephrine, epinephrine, and dopamine.
• MAOIs can be reversible or irreversible, and selective or non-selective.
• MAOIs primarily treat depression, panic disorder, and social anxiety.
• Sometimes prescribed for Parkinson's disease.

Mechanism of Action

• MAOIs inhibit monoamine oxidase (MAO) enzymes.
• MAO enzymes break down monoamine neurotransmitters.
• MAO inhibition increases neurotransmitter availability in the synaptic cleft.
• Increased neurotransmitter levels improve mood and reduce depression and anxiety.
• Two main types of MAO enzymes exist: MAO-A and MAO-B.
• MAO-A primarily metabolizes serotonin, norepinephrine, and epinephrine.
• MAO-B primarily metabolizes dopamine and phenylethylamine.
• Non-selective MAOIs inhibit both MAO-A and MAO-B enzymes.
• Selective MAOIs inhibit either MAO-A or MAO-B.

Types of MAOIs

• Non-Selective Irreversible MAOIs:
  • Inhibit both MAO-A and MAO-B.
  • These are older MAOIs.
  • Examples include phenelzine (Nardil), tranylcypromine (Parnate), and isocarboxazid (Marplan).
• Selective Reversible MAO-A Inhibitors (RIMAs):
  • Selectively inhibit MAO-A.
  • Considered safer than non-selective MAOIs.
  • An example is moclobemide (Manerix).
• Selective Irreversible MAO-B Inhibitors:
  • Selectively inhibit MAO-B.
  • Used in Parkinson's disease treatment.
  • An example is selegiline (Eldepryl).

Clinical Uses

• Treat depression, especially atypical depression.
• Manage panic disorder, social anxiety disorder, and other anxiety disorders.
• Treat Parkinson's disease (selective MAO-B inhibitors).
• Sometimes used for treatment-resistant depression when other antidepressants are ineffective.

Side Effects

• Common side effects include:
  • Orthostatic hypotension (sudden drop in blood pressure upon standing).
  • Weight gain.
  • Sexual dysfunction.
  • Sleep disturbances.
  • Dry mouth.
  • Constipation.
• Serious side effects:
  • Hypertensive crisis (severe increase in blood pressure).
  • Serotonin syndrome (especially when combined with other serotonergic drugs).
  • Liver damage (rare).

Hypertensive Crisis

• Hypertensive crisis is a severe, potentially life-threatening side effect of MAOIs.
• It is usually triggered by consuming foods or beverages high in tyramine.
• Tyramine, an amino acid, is normally broken down by MAO in the gut.
• When MAO is inhibited, tyramine can accumulate and cause a rapid increase in blood pressure.
• Symptoms include severe headache, stiff neck, nausea, vomiting, sweating, and rapid heartbeat.
• It can lead to stroke, heart attack, or death if untreated.
• Patients taking MAOIs must follow a strict diet to avoid tyramine-containing foods.

Dietary Restrictions

• Patients must avoid foods and beverages high in tyramine to prevent hypertensive crisis.
• Foods to avoid include:
  • Aged cheeses (e.g., cheddar, Swiss, blue cheese).
  • Cured or processed meats (e.g., salami, pepperoni, smoked fish).
  • Fermented foods (e.g., sauerkraut, kimchi, soy sauce).
  • Alcoholic beverages (especially beer and red wine).
  • Overripe fruits and vegetables.
  • Yeast extracts.
• Patients should also be cautious with certain medications that can interact with MAOIs, such as decongestants and some pain relievers.

Drug Interactions

• MAOIs interact with many medications, increasing the risk of serious side effects.
• Should not be combined with other antidepressants, especially SSRIs, SNRIs, and TCAs.
• Combining with other serotonergic drugs can lead to serotonin syndrome:
  • Characterized by confusion, agitation, muscle rigidity, hyperthermia, and autonomic instability.
  • Potentially fatal.
• MAOIs can also interact with certain pain medications, decongestants, and stimulants.
• Always consult a healthcare professional before taking any new medication while on an MAOI.

Precautions

• Patients with a history of cardiovascular disease, cerebrovascular disease, or hypertension should use MAOIs with caution.
• MAOIs should be avoided in patients with pheochromocytoma (a tumor of the adrenal gland) due to the risk of hypertensive crisis.
• Use caution in patients with a history of liver disease or seizure disorders.
• MAOIs should be discontinued gradually to avoid withdrawal symptoms.
• Patients should be monitored closely for side effects and drug interactions.

Overdose

• MAOI overdose can be life-threatening.
• Symptoms of overdose include:
  • Agitation.
  • Muscle rigidity.
  • Hyperthermia.
  • Seizures.
  • Coma.
• Treatment of MAOI overdose typically involves supportive care, including monitoring vital signs, managing hyperthermia, and controlling seizures.
• Activated charcoal may be administered to reduce drug absorption.
• Specific antidotes may be used to manage certain symptoms, such as hypertension or serotonin syndrome.

Discontinuation Syndrome

• Abrupt discontinuation of MAOIs can lead to a withdrawal or discontinuation syndrome.
• Symptoms of discontinuation syndrome may include:
  • Flu-like symptoms.
  • Insomnia.
  • Nausea.
  • Dizziness.
  • Anxiety.
  • Irritability.
• To minimize the risk of discontinuation syndrome, MAOIs should be tapered gradually under the supervision of a healthcare professional.

MAO and Neurodegenerative Diseases

• MAO-B inhibitors are used in the treatment of Parkinson's disease.
• By inhibiting MAO-B, these drugs increase dopamine levels in the brain.
• Increased dopamine can help improve motor function and reduce symptoms of Parkinson's disease.
• Research suggests that MAO inhibitors may also have neuroprotective effects.
• Neuroprotective effects could potentially slow the progression of neurodegenerative diseases like Alzheimer's and Parkinson's.

Current Research

• Current research focuses on developing new and safer MAOIs with fewer side effects and drug interactions.
• Scientists are exploring the potential of selective MAO inhibitors for treating more conditions, including:
  • Depression.
  • Anxiety disorders.
  • Cognitive impairment.
• Studies also investigate the neuroprotective effects of MAO inhibitors and their potential role in preventing or slowing the progression of neurodegenerative diseases.

Monoamine oxidase inhibitors (MAOIs) are drugs that inhibit monoamine oxidase enzymes, which break down neurotransmitters like serotonin and dopamine, increasing their availability in the brain. They are used to treat depression, panic disorder, social anxiety and sometimes Parkinson's disease. MAOIs can be reversible or irreversible, and selective or non-selective.