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The Comprehensive List of Antidepressants

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What is depression?

Occasional feelings of sadness or depression are experienced by most people at some point in life. Feeling sad is a normal human response to difficult situations such as loss of a loved one, financial troubles, or problems at home. These feeling usually last for a few days. However, when these feelings turn into intense sadness, or a person feels helpless, worthless, and hopeless, and last for weeks or longer, it could be due to clinical depression. Depression is a common but serious mental illness that affects millions of Americans. The symptoms of depression interfere with daily life and cause significant pain to the patient and their loved ones. Although with proper treatment even severe symptoms of depression can get better, many people never seek treatment due to the societal stigma associated with mental illnesses.

Common symptoms of depression include the following:

  • Sadness, unhappiness
  • Loss of interest in enjoyable activities
  • Anger, frustration, irritability
  • Sleep changes (too much or too little)
  • Feelings of worthlessness
  • Thoughts of death or suicide; suicidal attempts
  • Weight loss or weight gain

What are the classes of available antidepressants?

What are the members in each antidepressant class?

There are several different classes of antidepressant medications. Each one has a different mechanism of action and side effect profile.

Selective serotonin reuptake inhibitors (SSRIs)

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants. They are highly effective and generally cause fewer side effects than the other antidepressants. SSRIs help to alleviate symptoms of depression by blocking the reabsorption or reuptake of serotonin in the brain. Serotonin is a naturally occurring neurotransmitter (chemical) that is used by brain cells to communicate. As SSRIs mainly affect the levels of serotonin and not levels of other neurotransmitters, they are referred to as “selective.”

Selective serotonin reuptake inhibitors (SSRIs) include citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), fluvoxamine CR (Luvox CR), paroxetine (Paxil), paroxetine CR (Paxil CR), sertraline (Zoloft).

Side effects of SSRIs may include nausea, vomiting, diarrhea, sexual dysfunction, headache, weight gain, anxiety, dizziness, dry mouth, and trouble sleeping.

Although SSRIs are relatively safe, there are some safety concerns regarding their use.

  • Abnormal bleeding: Use of SSRIs with certain pain relievers (aspirin, ibuprofen [Motrin, Advil], naproxen [Naprosyn, Aleve], and blood thinners such as warfarin [Coumadin]) may increase the risk of bleeding.
  • Serotonin syndrome: Serotonin syndrome is a serious medical condition that can occur when medications that alter the concentration of serotonin in the brain are taken together. Symptoms of serotonin syndrome may include anxiety, restlessness, sweating, muscle spasms, shaking, fever, rapid heartbeat, vomiting, and diarrhea. Examples of medications that can cause serotonin syndrome include antidepressants, some pain relievers such as meperidine (Demerol) or tramadol (Ultram), St. John's wort, medicines used to treat migraine headaches called triptans, and some street drugs such as cocaine.

Significant Warnings

Suicidal thoughts or behavior: All antidepressants may increase the risk of suicidal thoughts or behavior in children, adolescents, and young adults (18 to 24 years of age).

Selective norepinephrine reuptake inhibitors (SNRIs)

Serotonin norepinephrine reuptake inhibitors (SNRIs) work by blocking the reabsorption of the neurotransmitters serotonin and norepinephrine in the brain. They may also have an effect on other neurotransmitters.

Serotonin-Norepinephrine Reuptake inhibitors (SNRIs) include desvenlafaxine (Pristiq), duloxetine (Cymbalta), venlafaxine (Effexor), venlafaxine XR (Effexor XR), milnacipran (Savella), and levomilnacipran (Fetzima).

Side effects most common to the class of SNRIs include nausea, dizziness, and sweating. SNRIs, particularly duloxetine, venlafaxine, and desvenlafaxine may cause sexual dysfunction. Other side effects include tiredness, constipation, insomnia, anxiety, headache, and loss of appetite.

Significant Warnings

  • Abnormal bleeding
  • Suicidal thoughts or behavior: All antidepressants may increase the risk of suicidal thoughts or behavior in children, adolescents, and young adults (18 to 24 years of age).

Contraindications

Duloxetine and milnacipran should not be used in patients with uncontrolled narrow angle or angle-closure glaucoma.

Tricyclic Antidepressants (TCAs)

Tricyclic antidepressants (TCAs) were one of the first approved antidepressants. Although they are effective, they have been replaced by newer antidepressants that generally cause fewer side effects. Like SNRIs, TCAs work by blocking the reabsorption of the neurotransmitters serotonin and norepinephrine in the brain. Additionally, they block muscarinic M1, histamine H1, and alpha-adrenergic receptors.

Tricyclic antidepressants (TCAs) include amitriptyline (Elavil), desipramine (Norpramin), doxepine (Sinequan), Imipramine (Tofranil), nortriptyline (Pamelor), amoxapine, clomipramine (Anafranil), maprotiline (Ludiomil), trimipramine (Surmontil), and protriptyline (Vivactil).

Side effects: TCAs affect several neurotransmitters in the brain and, as a result, cause numerous side effects. The most common side effects include dry mouth, constipation, blurred vision, urinary retention, dizziness, tachycardia, memory impairment, and delirium. Other side effects include orthostatic hypotension, weight gain, seizures, bone fractures, sexual dysfunction, increased sweating, and increased or irregular heartbeats.

Contraindication

TCAs should not be used within 14 days of taking an MAOI.

Significant Warning

Suicidal thoughts or behavior: All antidepressants may increase the risk of suicidal thoughts or behavior in children, adolescents, and young adults (18 to 24 years of age).

Monoamine oxidase inhibitors (MAOIs)

Monoamine oxidase inhibitors (MAOIs) block the activity of monoamine oxidase, an enzyme that breaks down norepinephrine, serotonin, and dopamine in the brain and other parts of the body. MAOIs have many drug and food interactions and cause significant side effects in comparison to the new antidepressants. As such, MAOIs have been replaced by newer antidepressants that are safer and cause fewer side effects.

Monoamine oxidase inhibitors (MAOIs) include phenelzine (Nardil), selegiline (Emsam), and tranylcypromine (Parnate).

Common side effects include postural hypotension, weight gain, and sexual side effects.

Significant Warnings

  • Hypertensive crisis: Taking MAOIs with tyramine-containing foods or beverages may cause dangerous elevations in blood pressure. Foods that should be avoided include wine, aged cheese, sauerkraut, cured meats, draft beer, soy products, and others.
  • Suicidal thoughts or behavior: All antidepressants may increase the risk of suicidal thoughts or behavior in children, adolescents, and young adults (18 to 24 years of age).

Atypical antidepressants

Atypical antidepressants are considered “atypical” because these agents do not fit into any of the other classes of antidepressants. Each medicine in this category has a unique mechanism of action in the body. However, like other antidepressants, atypical antidepressants affect the levels of dopamine, serotonin, and norepinephrine in the brain. Brintellix and Viibryd inhibit reuptakeof serotonin but also act on serotonin receptors.

Atypical antidepressants include bupropion (Wellbutrin), mirtazapine (Remeron), nefazodone (Serzone), trazodone (Desyrel, Oleptro), vilazodone (Viibryd), and vortioxetine (Brintellix).

Since medications in this class have unique properties, their side effect profile also varies. Some common side effects include dry mouth, constipation, dizziness, and lightheadedness.

  • Mirtazapine and trazodone cause drowsiness and are usually taken at bedtime.
  • Bupropion generally does not cause weight gain or sexual problems. Bupropion may also be used to help quit smoking.
  • Viibryd is not associated with significant weight gain or sexual dysfunction.

Safety concerns:

  • Mirtazapine and trazodone may cause abnormal heart rhythms that can be life threatening.
  • Trazodone may cause a rare sexual disorder called priapism, painful and prolonged erection in males.
  • Nefazodone may cause life-threatening liver failure. Generally, use of nefazodone is not recommended in patients with active liver disease.
  • Suicidal thoughts or behavior: All antidepressants may increase the risk of suicidal thoughts or behavior in children, adolescents, and young adults (18 to 24 years of age).

Contraindications

  • Bupropion should not be used in patients with seizure disorders, eating disorders, and within 2 weeks of using MAOIs.
  • Nefazodone should not be used in patients with active liver disease.

What are natural antidepressants?

Natural antidepressants are remedies that are not prescription medications for depression. They may be helpful in improving mood but should not be used to self manage clinical depression without the supervision of a doctor.

Exercise and pleasurable activities are natural ways to improve mood. Exercise increases the levels of endorphins which can elevate mood. Foods high in omega-3-fatty acids may increase serotonin levels in the brain and contribute to relieving depression. During winter months some people may suffer from seasonal depression. Increasing exposure to light alleviates seasonal depression.

Several supplements are promoted for improving depression. Examples include St. John's wort, 5-hydroxytryptophan (5-HTP), SAMe, fish oil, and L-theanine. Although these supplements may have mild antidepressant properties, it is important to remember that depression is a serious condition that needs proper evaluation and treatment under the care of a physician. It is also important to note that these supplements are not regulated by the FDA; their safety and efficacy have not been proven in large clinical studies, and they may interact with other drugs.

Further reading: common depressive disorders and related conditions

REFERENCES:

Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2009.

FDA Full Prescribing Information.

"Monomine oxidase inhibitors (MAOIs) for treating depressing adults.” UpToDate.

"Atypical antidepressant: Pharmacology, administration, and side effects.” UpToDate.

"Chapter 51. Major Depressive Disorder." Pharmacotherapy: A Pathophysiologic Approach.

Reviewed by:
Marina Katz, MD
American Board of Psychiatry & Neurology

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