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A Comparison of Ketamine vs. Traditional Antidepressants

Depression, anxiety, and other conditions are unfortunately common, affecting almost everyone at some point in their lives.  The good news is various treatment options prove highly effective – the two here we will be discussing are ketamine and traditional antidepressants. Traditional antidepressants include medications such as Zoloft, Prozac, Paxil, etc, which are used to treat conditions like depression, anxiety, obsessive-compulsive disorder, and other conditions.  Ketamine has traditionally been considered a second-line treatment to try once someone has tried and failed to benefit from the medications mentioned above.  Such patient care is considered to be treatment-resistant. In this article, you can learn how ketamine as an antidepressant works and how it compares with traditional antidepressants.


Representative images to illustrate a comparison of ketamine versus traditional antidepressants.

All About Antidepressants

First, let’s discuss traditional psychiatric medications. Antidepressants are commonly prescribed to treat depression, anxiety disorders, major depressive disorder (also known as bipolar disorder), PTSD, and other psychiatric disorders. If you present to your family medicine physician or a psychiatrist, they are typically the first treatment offered (sometimes alongside therapy) to help treat symptoms of depression, anxiety, etc.  You can take the medication for 6 months and then stop, or you can potentially stay on it for years.


Types of Antidepressants

There are several different types of antidepressants a person may be prescribed, including: 


SSRIs/SNRIs/DNRIs

This category encompasses the most commonly used categories of antidepressants.  These medications debuted in the 1990s and were groundbreaking when they were first released.   These medications can affect the levels of serotonin, norepinephrine, and dopamine in the brain.  Each has a slightly different effect profile, which can lead to differences in benefits, side effects, and use cases.  As a result, patients often undergo “titration,” in which they try one and then another until a medicine is found that maximizes benefit and minimizes side effects.  Approximately 1/3rd of patients benefit with no side effects, ⅓ benefit but have potentially limiting side effects, and 1/3rd experience no benefits.  SNRIs and DNRIs can have “activating” effects and can be beneficial when treating patients who also have ADHD or who suffer from low energy.


Examples of common medications in each class


SSRI

  • citalopram (Cipramil)

  • dapoxetine (Priligy)

  • escitalopram (Cipralex)

  • fluoxetine (Prozac or Oxactin)

  • fluvoxamine (Faverin)

  • paroxetine (Seroxat)

  • sertraline (Lustral)

  • vortioxetine (Brintellix)


SNRI

  • Desvenlafaxine (Pristiq)

  • Duloxetine (Cymbalta) 

  • Levomilnacipran (Fetzima)

  • Venlafaxine (Effexor XR)


DNRI

  • Bupropion (Wellbutrin, Zyban)


TCAs and MAOIs

Tricyclic antidepressants and Monoamine oxidase inhibitors are older medications that have an increased potential for side effects.  Nonetheless, they can still be prescribed and beneficial for some patients.



Antidepressant Side Effects

Some people who take antidepressants may experience side effects, especially in the beginning. Some of these symptoms include: 

  • Constitutional symptoms - Dizziness, Weight Gain or Loss

  • Sexual side effects - decreased libido, difficulty achieving orgasm

  • Headaches

  • GI side effects - nausea, diarrhea

  • Psychiatric symptoms - increased anxiety


Usually, these symptoms disappear over time. However, they may return if a person suddenly goes off an antidepressant (causing withdrawal symptoms). If the symptoms don’t disappear, the patient will likely speak to their doctor about changing medication. 


How Effective Are Traditional Antidepressants?

Antidepressants are widely prescribed for a reason – for many people, they are highly effective and affordable and help many patients live a happier, less stressful life when taking them. However, efficacy varies between individuals.  One patient might experience alleviated depression symptoms after taking antidepressants for just one month, while another may not experience any benefits; in fact, they might only find the antidepressants cause unpleasant symptoms without helping their depression at all. 

Sometimes, a patient goes through multiple types of antidepressants before finding the right one. In other cases, it may be realized that a patient does not respond well to antidepressants, which is often called treatment-resistant depression. 


All About Ketamine as an Antidepressant 

When most people hear ketamine, they think “horse or cat tranquilizer,” club drug, or Matthew Perry’s tragic overdose.  They are not the greatest associations.  That said, ketamine is on the WHO list of essential medications that are available in every country around the world.  Ketamine was traditionally used as an anesthetic during surgical procedures.  In the early 2000s, it was discovered to have potent activity as an antidepressant.  Since then, its use as an “off-label” treatment for depression, anxiety, and other conditions has exploded.  A specific formulation of ketamine, in a nasal spray called Spravato, was approved for the treatment of major depression by the FDA in 2019 and is the only form of ketamine that is reimbursed by insurance.  Even though Spravato tends to be less effective than intravenous or intramuscular ketamines, it has grown rapidly in popularity because it can be covered by some(but not all)  insurance plans..


Typically, ketamine is given as an intravenous infusion under medical care, but nasal sprays and intramuscular injections are also used. Unlike traditional antidepressants, which take weeks to kick in, the antidepressant benefits from ketamine treatment can be felt in a matter of hours to days.


Intravenous therapy tends to be the most effective, followed closely by intramuscular treatment.  Nasal sprays and oral treatments are significantly less effective but can still offer benefits.


How Does Ketamine Work as an Antidepressant?

Ketamine offers an entirely different mechanism of action from traditional antidepressants like SSRIs and the like.  Ketamine works at many different brain receptors and can boost brain-derived neurotrophic factor (BDNF), which helps the brain’s neurons develop new connections. As a result, Ketamine as an antidepressant can work when many other medications have failed


Potential Side Effects of Ketamine as an Antidepressant

It’s important to note that ketamine has few long-term side effects.  The most significant side effect that long-term medical use (over 100 treatment sessions) can result in is damage to the bladder, which can manifest as the increased urge to urinate and blood in the urine.  These changes are almost universally reversible once ketamine treatment is stopped.

The treatments themselves can have temporary side effects that last for a few hours, including


  • Feeling Drowsy

  • Nausea

  • Visual hallucinations

  • Headaches

  • Anxiety (mainly a secondary effect of the hallucinations)

  • Dizziness 


There are some more adverse effects of taking ketamine that aren’t nearly as common, including triggering manic episodes – it’s important to speak to your medical provider about any side effects you are concerned about. 


Ketamine vs Antidepressants: Which is Better? 

Trick question!  There is no better.  It depends on the individual, their needs, and their preference.  Both ketamine and antidepressants can treat depression and anxiety. Some people find that traditional antidepressants work well for their depression or anxiety (or both), and will not need to seek further treatment like ketamine. However, ketamine treatment is often recommended for patients with depression who are resistant to typical treatments. 


Traditional Antidepressants

Benefits

  • Widely available

  • Covered by insurance

  • Generic versions are very affordable, even if you don’t have insurance


Drawbacks

  • You have to take a pill every day

  • It can take a long time to take effect (minimum 2 weeks, up to 6 weeks)

  • Side effects can limit benefits or make them difficult to take

  • Some people experience difficult symptoms such as increased anxiety, insomnia, etc, as they taper off these medications


Ketamine

Benefits

  • Works rapidly

  • You can take it as needed (no need to taper on or off) when you experience depression or anxiety

  • It can significantly increase neuroplasticity, which, when combined with therapy and other interventions, can lead to permanent beneficial changes in thought and behavior

  • It can work when multiple other medications have failed


Drawbacks

  • It's expensive

  • It can be logistically challenging to arrange visits for treatments

  • The experience of ketamine can be difficult for patients not accustomed to altered states

  • Side effects can limit benefits or make them difficult to take


What About Psychedelics?

There has been a rapid uptick in interest in using psychedelics for mental health conditions.  While many of these substances have been associated with recreational use dating back to the 1960s, a growing body of research suggests that they have potent benefits for mental health.  Such substances include psilocybin (the active compound in mushrooms), MDMA, LSD, DMT (the active compound in ayahuasca), and many other molecules.

Psychedelics are still federally illegal, but some states, such as Colorado, are starting to legalize psychedelics for use locally.  We anticipate that many more states will do so. At some point, the federal government will likely approve specific pharmaceutical formulations of psychedelic molecules for use in mental health conditions.  While we can’t currently offer psychedelic medicines legally, ketamine mirrors many of the benefits of traditional psychedelics.  Additionally, we are deeply familiar with cutting-edge research in psychedelics and can help patients understand how these substances may benefit them.  


Ketamine vs Antidepressants: The Takeaway

It can be challenging to deal with long-term mental health conditions. Typically, the first action a doctor or psychologist will take with a person with depression or other mood disorders is an antidepressant prescription. While this can be effective for many, some patients will be reluctant to take a daily medication, they may find side effects limiting,  may simply not benefit or may want a faster acting medicine.  Ketamine offers an attractive alternative to such individuals.  Finally, ketamine can be combined with traditional antidepressants as it plays very well in the “sandbox” with other medications, so it really isn’t an either-or.


Are you interested in ketamine treatment or another kind of alternative medicine? At Daydream MD, we provide a range of depression treatments to help you heal. We have excellent mental health professionals on our side who will help you recover, whether that’s through psychedelic therapy, ketamine treatments, wellness coaching, or individual therapy. We take a collaborative approach to mental health in which we spend time understanding what you're dealing with and your treatment preferences, provide a menu of options, and develop a plan of care together.  Get in touch with our friendly team today to get started.

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