Ketamine Therapy vs. Antidepressants: What Are The Pros And Cons Of Each?

Ketamine Therapy vs. Antidepressants: What Are The Pros And Cons Of Each?

Depression is one of the most common mental health issues in the world — and alternative options like ketamine therapy is becoming a serious treatment option. With depression characterized as feelings of hopelessness, a lack of joy, and persistent sadness, clinical depression affects a staggering 280 million people worldwide.

The good news is that there are many treatments for depression, from talk therapy to medication. Recently, some fascinating research has suggested that certain psychedelic drugs may have antidepressant effects. This is exciting news for those who haven’t had luck with conventional treatments for depression.

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Ketamine therapy is one of the treatments many are seeking as an alternative to traditional antidepressants. But how does it compare? When it comes to ketamine therapy vs. antidepressants, what should you know? Are there benefits to ketamine therapy that other antidepressants do not have?

Here, we weigh the pros and cons of ketamine therapy vs. antidepressants.

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Safety and Side Effects Comparison Chart

Treatment TypeSafety ProfileCommon Side Effects
Ketamine TherapyGenerally considered safe under medical supervision. Risk of abuse and dependency.Dissociation, nausea, vomiting, dizziness, increased heart rate and blood pressure.
SSRIsWell-tolerated with low risk of serious side effects. Low risk of overdose.Nausea, sexual dysfunction, headache, sleep disturbances, anxiety.
SNRIsGenerally well-tolerated. Possible increase in blood pressure.Similar to SSRIs, with more severe nausea and insomnia, dry mouth.
TCAsHigher risk of overdose. Can affect heart rhythm.Drowsiness, dry mouth, blurred vision, constipation, urinary retention.
MAOIsRisk of severe dietary and drug interactions. Less commonly prescribed due to safety concerns.Dry mouth, dizziness, digestive issues, insomnia, hypertensive crisis with certain foods.
Atypical AntidepressantsVaries per medication. Generally safe but can have unique side effects.Varies widely; drowsiness, weight gain, nausea, sexual dysfunction (in some types).


Before diving into the pros and cons of conventional antidepressants, we should first consider that antidepressants fall into five major classes. These include the following.

  • Selective Serotonin Reuptake Inhibitors (SSRIs)
  • Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)
  • Tricyclic Antidepressants (TCAs)
  • Monoamine Oxidase Inhibitors (MAOIs)
  • Atypical Antidepressants

Each of these classes comes with its own set of benefits and potential adverse effects. We discuss them individually below to give you the pros and cons of each specific class.


Medical professionals commonly prescribe SSRIs because of their effectiveness. Many experts believe low levels of serotonin in the brain causes depression. SSRIs work by increasing levels of serotonin in the brain.


SSRIs are preferred over other classes of antidepressants because people tolerate them better, and they are associated with fewer side effects. The possibility of an overdose being fatal is also highly unlikely when taken alone.


One of the drawbacks of using SSRIs is that most people will experience side effects when they first start taking them. Although they are often mild, they may be distressing to some. These include the below.

  • Nausea and vomiting
  • Sexual dysfunction
  • Anxiety or feeling shaky
  • Dizziness
  • Blurred vision
  • Headache
  • Sleeping problems
  • Dry mouth

Older people should take caution when taking SSRI because it can cause their sodium levels to drop — a potentially dangerous condition called hyponatremia.

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A rare but more severe side effect is serotonin syndrome. It occurs when serotonin levels in the brain are too high. Extremely high levels of serotonin won’t make you feel any happier — in fact, it can be dangerous. This condition requires immediate medical attention. Symptoms include confusion, shivering, agitation, diarrhea, and in severe cases, unconsciousness.


SNRIs are similar to SSRIs, as there is no evidence that one works better than the other. However, some people reap better results from SNRIs and others respond well to SSRIs.


They may work for people who don’t respond to SSRIs.


The disadvantages of SNRIs are similar to the potential side effects of SSRIs. However, dry mouth, nausea, and insomnia are more severe and frequent than with SSRIs. In rare cases, SNRI can cause high blood pressure.


TCAs are an older class of antidepressant drugs. They are not the first treatment choice, but doctors may prescribe them to individuals who don’t respond to other therapies.


TCAs may be more effective at treating major depressive disorder (MDD) than SSRIs, and they are often prescribed for off-label conditions such as chronic pain and bulimia.


One of the major drawbacks of TCAs is that an overdose is almost always fatal. Other serious adverse effects include heart arrhythmias and problems with the central nervous system.

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Rarely prescribed, only specialist doctors should prescribe MAOIs. These are only an option for patients who don’t respond to other medications.


Patients with phobic disorders and forms of depression with atypical features (e.g., hysterical features) may benefit from MAOIs.


The use of MAOIs is associated with severe side effects, dietary and drug interactions, and safety concerns. The most frequent side effects are the following.

  • Dry mouth
  • Diarrhea
  • Constipation
  • Nausea
  • Feeling drowsy
  • Dizziness
  • Lightheadedness
  • Insomnia

MAOIs also tend to interact with foods containing tyramine (like nuts, cured meats, and aged cheeses) which can ultimately lead to death.

Atypical Antidepressants

Atypical antidepressants are a group of antidepressants that do not fit into any of the other classes of antidepressants. Each of the medications in this class has unique features, so their side effects are slightly different.


Each type of atypical antidepressant has unique benefits, as the below highlights.

  • Bupropion can help treat seasonal affective disorder and also help with smoking cessation.
  • Mirtazapine and Nefazodone can help manage major depression.
  • Trazodone can help patients with depression and anxiety or a combination of both.
  • Vilazodone and Vortioxetine can be useful to treat MDD.


Atypical antidepressants have common side effects such as dry mouth, dizziness, and lightheadedness. Mirtazapine and trazodone can cause drowsiness.

Mirtazapine can also cause weight gain and high cholesterol levels.

They can also cause safety issues in people with seizure disorders, heart problems, and eating disorders. Patients with these conditions should disclose them to their doctor as these medications may not be suitable for them to use.

RELATED: What Does Ketamine Feel Like?

Ketamine Therapy

Ketamine therapy is a relatively new treatment option for depression. While the drug has been around for decades, only recently has it been approved for treating depressive conditions.

There are two main types of ketamine therapy.

  • Racemic ketamine is the original form approved by the Food and Drug Administration (FDA). This fast-acting drug is usually used as an anesthetic. Most research on ketamine looks at racemic ketamine infusions.
  • Esketamine is a form of ketamine that first emerged in 2019. It’s sold as a nasal spray under the brand name Spravato, and is specific for depression treatment. In comparison to racemic ketamine, esketamine can be used at lower doses to achieve clinical results.


Compared to other drugs used for depression, side effects associated with ketamine are very mild. It also works faster than other antidepressants.

While it may take months before conventional antidepressants are effective, some patients already see improvements immediately after the first ketamine treatment.

Another feature of ketamine therapy that may give patients peace of mind is the safety. Doctors must administer the drug in a ketamine clinic setting while observing the patient. If they were to experience any negative reaction, they would be in a safe environment and receive the necessary care.


Esketamine is FDA-approved for treatment-resistant depression and major depressive disorder with suicidal thoughts or actions. However, racemic ketamine does not have FDA approval for depression. Both are available to use off-label to treat depression — so it is legal to use ketamine for depression treatment. However, insurance companies don’t cover ketamine infusions, and they can be expensive.

As a psychedelic, ketamine effects things like your mind and body in different ways. These include visual distortions, drowsiness, nausea, dizziness, increased heart rate and blood pressure, and vertigo.

RELATED: How Much Is Ketamine Therapy, And How Can You Pay?

Sian Ferguson

View all posts by Sian Ferguson

Sian Ferguson is a freelance writer based in Cape Town, South Africa and she has written for publications such as Healthline, Greatist, and Psych Central to name a few.

Her work focuses on health and wellness, and she's particularly passionate. She believes health content should inform and empower readers, not confuse them!

Abid Nazeer

This post was medically approved by Abid Nazeer

Dr. Nazeer is the Founder and President of APS Ketamine/Advanced Psychiatric Solutions, which he established in 2016 as the first psychiatric outpatient ketamine clinic in Illinois. He is board certified in Psychiatry as well as Addiction Medicine. He completed his psychiatry residency at Louisiana State University Health Sciences in Shreveport where he held the role of Chief Resident. Dr. Nazeer is providing medical oversight to the growth plan of Wesana Clinics, with the model of comprehensive psychiatry clinics specialized ketamine and psychedelic therapies, integrated brain health and wellness centers, and technology utilization of Wesana Solutions remote patient monitoring product.

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Comments (1)

  • Luke Smith
    October 9, 2023 at 5:56 am Reply

    It’s great that you mentioned how the side effects associated with ketamine are very mild compared to other drugs used for depression. I was watching an educational show earlier and it showed the various ways of dealing with depression. From what I’ve seen, it seems a lot of people opt for ketamine treatment services now, which seems pretty effective.

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