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Navigating Antidepressants: Types, How They Work & What to Expect

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Major depression is one of the most common mental health disorders. Approximately 19 million adults in the United States had at least one major depressive episode in 2019, representing 7.8% of all U.S. adults. More women than men suffer from this condition, and depression is also more common among people aged 18 to 25 years old.

Treatment for depressive disorders usually involves a combination of psychotherapy along with antidepressants. You may need to try several medications or dosages, or a combination of medications to find a treatment that works well for you.

How Do Antidepressants Work Scientifically?

Many of these medications impact your mood by affecting chemicals in the brain called neurotransmitters.

These neurotransmitters include serotonin (5-HT), norepinephrine (NE), and dopamine (DA). Low levels of these neurotransmitters have been associated with depression and decreased mood. Many antidepressants can raise these neurotransmitter levels in the brain, and may alleviate the symptoms of depressive disorders.

Antidepressant Medications

The medications most frequently used to treat depression are, not surprisingly, referred to as antidepressants. The major classes of antidepressants are:

  • Selective serotonin reuptake inhibitors (SSRIs)
  • Serotonin-norepinephrine reuptake inhibitors (SNRIs)
  • Tricyclic antidepressants (TCAs)
  • Monoamine oxidase inhibitors (MAOIs)
  • Atypical antidepressants

Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs are often first-line medications for depression because of their effectiveness in reducing the symptoms of depression and overall safety. What do SSRIs do? SSRIs block the reabsorption of serotonin (a neurotransmitter associated with depression) by the nerve cells. Therefore, more serotonin remains in the brain and can stimulate the nerve cells for a longer period.

The most commonly used SSRIs in the United States are:

  • Sertraline – Zoloft
  • Escitalopram – Lexapro
  • Fluoxetine – Prozac
  • Citalopram – Celexa
  • Paroxetine – Paxil, Paxil CR, Pexeva

SSRIs are oral medications available as tablets, capsules, or liquid solutions. They are usually administered once a day in the morning or at night. Most can be taken with or without food.

Common side effects from SSRIs include sexual dysfunction, trouble sleeping, weight changes, anxiety, dizziness, dry mouth, headache, and gastrointestinal (GI) distress.

Serotonin-Norepinephrine Reuptake Inhibitors (SNRI)

Norepinephrine is another neurotransmitter that has been linked to depression. SNRIs block the reabsorption (reuptake) of both serotonin and norepinephrine to increase these neurotransmitters’ activity in the brain and prolong their effect.

SNRI medications in use in the United States are:

  • Duloxetine – Cymbalta
  • Venlafaxine – Effexor, Effexor XR
  • Levomilnacipran – Fetzima
  • Desvenlafaxine – Pristiq

These oral-tablet medications are usually taken once a day, though this may vary depending on the specific medication. For example, venlafaxine may be dosed multiple times per day. Your healthcare provider may start with a lower dose and increase if necessary.

Side effects with SNRIs are similar to those with SSRIs, but SNRIs may also cause nausea, constipation, anxiety, loss of appetite, sweating and blood pressure changes.

Tricyclic Antidepressants (TCA)

Although effective options in depression, TCAs are usually not first-line medications for treating depression due to higher rates of side effects. However, they may be an option for people who do not respond to SSRI or SNRI treatment.

Similar to SNRIs, TCAs block the reuptake of norepinephrine and serotonin to reduce the symptoms of depression. However, tricyclic antidepressants also affect other chemical messengers such as acetylcholine and histamine.

The TCAs in use in the United States are:

  • Amoxapine – Asendin
  • Amitriptyline – Elavil
  • Desipramine – Norpramin
  • Nortriptyline – Pamelor
  • Doxepin – Sinequan
  • Trimipramine – Surmontil
  • Imipramine – Tofranil
  • Protriptyline – Vivactil
  • Maprotiline – Ludiomil (a tetracyclic antidepressant)

TCAs are available as oral tablets, capsules, and solutions. Common adverse events include constipation, dizziness, sedation and dry mouth. Many of the side effects result from their action on acetylcholine and histamine systems.

Monoamine Oxidase Inhibitors (MAOIs)

MAOIs were the first antidepressants developed, and although they can be very effective, they have been replaced by other antidepressants that cause fewer side effects. MAOIs have potential drug-drug interactions and drug-food interactions, further limiting their use and safety. However, MAOIs can be an option for patients who do not respond to other treatment options.

The monoamine oxidase enzyme is responsible for breaking down several neurotransmitters, including norepinephrine, serotonin, and dopamine. MAOIs block this enzyme, increasing these neurotransmitter levels in the brain.

MAOIs available in the USA are:

  • Selegiline – Emsam (skin patch)
  • Isocarboxazid – Marplan
  • Phenelzine – Nardil
  • Tranylcypromine – Parnate

MAOIs are usually administered orally, but selegiline is available as a skin patch. Drug labels for these medications list side effects such as dry mouth, nausea, diarrhea, constipation, drowsiness, insomnia, and dizziness, as well as severely high blood pressure if taken with the wrong foods or other medications.

Atypical Antidepressants

Atypical antidepressants don’t fit into any other group of antidepressants. They treat depression by changing the levels or sensitivity to one or more neurotransmitters such as serotonin, norepinephrine, or dopamine.

Examples of atypical antidepressants are:

  • Bupropion – Wellbutrin, Wellbutrin SR, Wellbutrin XL
  • Mirtazapine – Remeron
  • Trazodone – Desyrel
  • Nefazodone
  • Vilazodone – Viibryd
  • Vortioxetine – Trintellix

Bupropion and mirtazapine are oral medications often recommended as a first-line treatment for depressive disorders.

Genetic Testing for Antidepressants

Your clinician will work with you to determine what treatment options may be the most beneficial in reducing your symptoms. However, antidepressants are not a one-size-fits-all solution. About 30-50% of patients with major depressive disorder do not respond to their first antidepressant trial. Additionally, up to 33% of patients do not show significant improvement despite trying several medications.

Gene mutations may affect the likelihood of medication response and tolerability or how the body processes certain medications. Genetic testing for antidepressants can give your healthcare provider further information to use in their decision making process when selecting psychiatric medications.

PGx Testing Provides Helpful Information

Pharmacogenetic (PGx) testing examines your genes to identify DNA that can affect your ability to break down certain medications or make you more sensitive to some medications. One meta-analysis showed that patients that had genetic testing were 71% more likely to find effective medications compared to those that didn’t get tested.

Genomind PGx testing looks at 24 genes related to mental health treatment. It provides guidance across 10+ mental health conditions, including depressive disorders, and examines 130+ medications to help clinicians determine:

  • Which medications may be more or less likely to be effective
  • Which medications may be more or less likely to show side effects
  • How you metabolize medications for personalized dosing guidance

Genomind’s testing can be done at a clinician’s office—or from the comfort of your home. Get started today.

Starting Antidepressants

For individuals experiencing the symptoms of a depressive disorder, these are just some of the medication treatment options available. If you are exploring treatment options, discuss pharmacogenetic testing with your healthcare clinician to receive more personalized guidance. This test aims to minimize the time spent on trial and error, and help you get appropriate medication sooner.

Disclaimer: This page is for information purposes only. We cannot make recommendations about your unique situation, so always consult your healthcare provider for prescription choices.

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