SSRIs. SNRIs. TCAs. MAOIs.

Entering the world of antidepressants may feel a bit like wading into alphabet soup. If this is the first time your healthcare provider is discussing prescription medication for treating your major depressive disorder (MDD), understanding what they are recommending and why they are recommending it may be challenging.

There is much we still don’t understand about depression and how to treat it. For example, it had been believed that MDD was simply a chemical imbalance in the brain; however, scientists believe it’s more complicated than that.

“It is not possible to explain either the disease or its treatment based solely on levels of neurotransmitters,” Yale University neurobiologist Ronald Duman told Psychology Today.

In fact, Psychology Today states “the newest evidence indicates that recurrent depression is in fact a neurodegenerative disorder, disrupting the structure and function of brain cells, destroying nerve cell connections, even killing certain brain cells, and precipitating cognitive decline.”

Because so much is unknown about the disease and how to treat it, there are a variety of different depression treatments – including medication, psychotherapy (talk therapy), brain stimulation therapy, acupuncture, vagus nerve stimulation, and many others.

One of the most commonly used treatment options is antidepressant medications.

What are the Types of Depression Medications?

There are many different types of antidepressants:

• selective serotonin reuptake inhibitors (SSRIs)
• serotonin and norepinephrine reuptake inhibitors (SNRIs)
• tricyclic antidepressants (TCAs)
• monoamine oxidase inhibitors (MAOIs)
• ketamine

SSRIs and SNRIs

SSRIs

The most commonly used antidepressants are SSRIs. Serotonin is an important chemical associated with feelings of happiness and well-being, among other complex biological functions. SSRIs are designed to block the serotonin transporter, leading to an increase in serotonin in the synapse.

“Although serotonin has multiple functions in the brain, one of them is to keep us calm and content. So, when too little serotonin is active outside our brain cells, we become nervous, unhappy or unable to feel any pleasure,” writes Berit Brogaard D.M.Sci., Ph.D. in Psychology Today. “Blocking the transporter that inactivates serotonin can thus restore our brain’s levels of active serotonin and once again make us calm and content.”

Examples of SSRIs include fluoxetine (Prozac®), sertraline (Zoloft®), paroxetine (Paxil®), citalopram (Celexa®), fluvoxamine (Luvox®), and escitalopram (Lexapro®).

SNRIs

SNRIs are the second most commonly used antidepressants. Like SSRIs, they block the serotonin transporter, leading to an increase in the levels of serotonin in the synapse. In addition to that, they also block the norepinephrine transporter, leading to an increase in levels of norepinephrine in the synapse. According to the Mayo Clinic, SNRIs are thought to alleviate depressive symptoms by “impacting chemical messengers (neurotransmitters) used to communicate between brain cells.”

Desvenlafaxine (Pristiq®, Khedezla®), duloxetine (Cymbalta®) and venlafaxine (Effexor®) are some common SNRIs.

Tricyclic antidepressants (TCAs)

Other kinds of antidepressants are typically prescribed if SSRIs and SNRIs fail to alleviate depressive symptoms. TCAswork in a slightly similar way to SNRIs. They work to “block the reabsorption of serotonin and epinephrine back into nerve cells after these chemicals are released into a synapse,” according to WebMD.

Some examples of TCAs are amitriptyline (Elavil®), desipramine (Norpramin®), and clomipramine (Anafranil®).

Monoamine oxidase inhibitors (MAOIs)

MAOIs, the first antidepressants, were developed in the early 1950s.

“An enzyme called monoamine oxidase is involved in removing the neurotransmitters norepinephrine, serotonin and dopamine from the brain,” according to the Mayo Clinic. “MAOIs prevent this from happening, which makes more of these brain chemicals available to effect changes in both cells and circuits that have been impacted by depression.”

Isocarboxazid (Marplan®) and phenelzine (Nardil®) are two examples of MAOIs.

Ketamine

A new depression treatment, ketamine, has been receiving a lot of attention due to a recent Food & Drug Administration (FDA) regulatory approval decision. In March 2019, the FDA approved the use of esketamine nasal spray (Spravato®), in conjunction with an oral antidepressant, to treat patients with treatment-resistant depression.

According to Psychiatrist Alexander Papp, MD, in a Q&A for UC San Diego Health, ketamine “works by quickly increasing the activity of the neurotransmitter glutamate in the frontal cortex of the brain, while also allowing new synapses to form in the same area. The speediness of ketamine in producing an antidepressant effect occurs because this drug bypasses the traditional serotonin route and goes directly to activating glutamate. This is very different from traditional antidepressants, which first increase the activity of serotonin in multiple different areas of the brain, and then ultimately affect glutamate.” 

Finding an Antidepressant that Works for You

Depression medication doesn’t cure depression; it relieves the symptoms that depression can cause. Therefore, depression may require long-term treatment.

If you are having trouble finding a depression medication that alleviates your symptoms without causing frustrating side effects, you aren’t alone. Only about a third of patients who are diagnosed with major depressive disorder (MDD) find a medication that works for them on the first try.

Your healthcare provider takes into consideration your entire clinical profile for medication selection when prescribing medication, which can include:

• your symptoms
• potential side effects from the medication
• potential drug/drug interactions
• food/drug interactions
• other health conditions you have
• insurance coverage and/or cost

Additionally, your healthcare provider can also use pharmacogenomic testing as an additional tool. Tests like the GeneSight Psychotropic test may help healthcare providers determine how your unique DNA may impact how your body metabolizes and/or responds to certain antidepressants.

Once you and your doctor have chosen a medication regimen, it’s important to keep in touch. You should notify your healthcare provider of any side effects, or if the medication isn’t relieving your symptoms.

However, as the Mayo Clinic warns, “it may take six or more weeks for it to be fully effective. With some antidepressants, you can take the full dosage immediately. With others, you may need to gradually increase your dose.” The Mayo Clinic further cautions that you should take your medication as prescribed by your healthcare provider – consistently and at the correct dosage.

If you are interested in learning more about antidepressant treatments, please read our other blog posts “How to Minimize Antidepressant Side Effects” or “Is Your Antidepressant Working? 4 Ways to Tell.”