Monoamine Oxidase Inhibitors (MAOIs) vs. Selective Serotonin Reuptake Inhibitors (SSRIs)

• Monoamine oxidase inhibitors (MAOIs) and selective serotonin reuptake inhibitors (SSRIs) are types of antidepressants used to treat depression.
• MAOIs are an older class of antidepressants that are not used as much because of drug and food interactions. MAOIs also are used to treat Parkinson's disease.
• SSRIs are also used to treat anxiety.
• Examples of MAOIs include rasagiline (Azilect), selegiline (Eldepryl, Zelapar, Emsam), isocarboxazid (Marplan), phenelzine (Nardil), and tranylcypromine (Parnate).
• Examples of SSRIs include citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, Symbyax), fluvoxamine (Luvox, Luvox CR), paroxetine (Paxil, Paxil CR, Pexeva), sertraline (Zoloft), and vilazodone (Viibryd).
• Side effects of monoamine oxidase inhibitors (MAOIs) and selective serotonin reuptake inhibitors (SSRIs) that are similar include nausea, vomiting, headache, agitation, sexual dysfunction, and weight changes.
• Side effects of monoamine oxidase inhibitors (MAOIs) that are different from selective serotonin reuptake inhibitors (SSRIs) include dizziness on standing, lack of strength, weakness, dizziness, drowsiness, fatigue, abnormal movements, dry mouth, abdominal pain, anxiety, and mood or behavior changes.
• Side effects of selective serotonin reuptake inhibitors (SSRIs) that are different from monoamine oxidase inhibitors (MAOIs) include insomnia, diarrhea, restlessness, and increased blood pressure.

Monoamine oxidase inhibitors (MAOIs) were the first class of antidepressants developed. They fell out of favor because of concerns about interactions with certain foods and numerous drug interactions. MAOIs elevate levels of the neurotransmitters norepinephrine, serotonin, and dopamine in the brain by inhibiting an enzyme called monoamine oxidase. Monoamine oxidase breaks down norepinephrine, serotonin, and dopamine. When monoamine oxidase is inhibited, norepinephrine, serotonin, and dopamine are not broken down, increasing the concentration of all three neurotransmitters in the brain. MAOIs also are used to treat Parkinson's disease.

Selective serotonin reuptake inhibitors (SSRIs) are a type of antidepressant used to treat depression. Some SSRIs may be used to treat anxiety. SSRIs are the most widely used class of antidepressants. They work by increasing the level of serotonin in the brain. Unlike MAOIs and tricyclic antidepressants (TCAs), SSRIs do not significantly affect norepinephrine levels in the brain. SSRIs also have fewer and milder side effects, fewer drug interactions, and are much less likely to be associated with suicide than TCAs.

MAOIs

Since MAOIs work in the brain and affect neurotransmitters, they have many side effects. Side effects of MAOIs are:

• Sudden drop in blood pressure upon standing up (orthostatic hypotension)
• Lack of strength
• Weakness
• Nausea
• Vomiting
• Dizziness
• Drowsiness
• Headache
• Fatigue
• Agitation
• Abnormal voluntary movement
• Dry mouth
• Abdominal pain
• Anxiety
• Change in mood or behavior
• Weight gain
• Impotence (erectile dysfunction, ED)

MAOIs also carry boxed warnings of suicidal thinking and suicidal behavior in children, adolescents, and young adults.

SSRIs

• Headaches: SSRIs cause headaches and dose-related nausea, vomiting, and diarrhea that improve with continued treatment.
• Insomnia, restlessness, agitation: Insomnia, restlessness, and agitation-which decrease over time-also are associated with SSRIs. Insomnia can be treated with low dose (50-100 mg) trazodone (Desyrel) at bedtime and agitation may be managed by reducing the SSRI dose or treating with anti-anxiety drugs.
• Sexual dysfunction: SSRIs also are associated with sexual dysfunction. Symptoms of sexual dysfunction in men may be treated with sildenafil (Viagra), yohimbine (Pausinystalia yohimbe), amantadine (Symmetrel), cyproheptadine, or neostigmine (Prostigmin).
• Weight gain or loss: Over time, weight loss or weight gain has been associated with SSRIs. Patients may experience weight loss initially but quickly regain weight.

MAOIs

MAOIs may come in oral tablet form. Rasagiline (Azilect), for example, is a common MAOI. The recommended dose of rasagiline is 1 mg once daily when used alone (monotherapy). When combined with levodopa the recommended starting dose is 0.5 mg once daily. The dose may be increased to 1 mg once daily if the response is not adequate. Patients with mild liver disease should not use more than 0.5 mg daily. It should not be used by patients with moderate or severe liver disease. Tyramine rich food, beverages and supplements should be avoided while taking rasagiline.

SSRIs

SSRIs are often supplied in tablet or capsule form. For example, depression in adults is treated with 20-80 mg of fluoxetine (Prozac), a common SSRI, daily. The recommended dose for treating depression in children is 10-20 mg daily. After 13 weeks of daily administration, 90 mg once weekly may be effective in some patients.

MAOIs

MAO inhibitors should be avoided with other antidepressants such as paroxetine fluoxetine, amitriptyline, nortriptyline, bupropion; pain medications like methadone, tramadol, and meperidine; dextromethorphan, St. Johns Wort, cyclobenzaprine, and mirtazapine. Such combinations lead to high serotonin levels which may lead to confusion, high blood pressure, tremor, hyperactivity, coma, and death. These medications should not be used within 14 days of stopping an MAOI.

MAOIs also interact with seizure medications like carbamazepine (Tegretol Tegretol XR, Equetro, Carbatrol)and oxcarbazepine (Trileptal) through unknown mechanisms, increasing side effects.

MAOIs are not recommended for use with medications like pseudoephedrine, phenylephrine, ephedrine, and phenylpropanolamine. The combination of MAO inhibitors and these drugs can cause an acute hypertensive episode.

Monoamine oxidase also breaks down tyramine, a chemical present in aged cheese, wines, and other aged foods. Since MAOIs inhibit monoamine oxidase, they decrease the breakdown of tyramine from ingested food, thus increasing the level of tyramine in the body. Excessive tyramine can elevate blood pressure and cause a hypertensive crisis. Patients treated with MAOIs should adhere to recommended dietary modifications that reduce the intake of tyramine.

SSRIs

• Confusion, high blood pressure, tremor, hyperactivity, coma, and death may occur when SSRIs are combined with other drugs that increase brain serotonin levels, for example, MAOIs, TCAs, sumatriptan (Imitrex), linezolid (Zyvox), St John's Wort, tramadol (Ultram), and meperidine (Demerol).
• The risk of gastrointestinal bleeding may be increased when SSRIs are combined with nonsteroidal anti-inflammatory drugs (NSAIDs).
• SSRIs may increase the effect of the blood thinner warfarin (Coumadin, Jantoven), leading to excessive bleeding. Therefore, warfarin therapy, and patients taking NSAIDs should be monitored more frequently with PT/INR testing in individuals who also are taking SSRIs.

MAOIs

• The FDA classifies MAO inhibitors in pregnancy category C, which means that there is no established evidence of safe and effective use of MAO inhibitor in pregnant women. Therefore, infant risk cannot be ruled out.
• It is not known whether MAO inhibitors enter breast milk; however, MAO inhibitors should be avoided in nursing mothers to avoid harm to the fetus.

SSRIs

• The safety of SSRIs during pregnancy and breastfeeding has not been established. Therefore, they should not be used during pregnancy unless, in the opinion of the physician, the expected benefits to a patient outweigh unknown hazards to the fetus.
• Many SSRIs are excreted in human milk. They should not be given to nursing mothers unless, in the opinion of the physician, the expected benefits to the patient outweigh the possible hazards to the child.