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How it works

How does the Ketamine infusions work?

When a person has depression, the most go-to interventions used for their treatment are psychotherapeutic such as CBT. Aside from therapy, patients are also given antidepressants such as Zoloft, Sert, Prozac, etc.

 

But unfortunately, only a handful of people respond to pills.

And when people don’t respond to this class of medicine for more than two trials, they're then diagnosed with treatment-resistant depression. No matter how many bottles of pills they empty, it’s not going to help them.

 

After reaching this dead-end during the treatment of depression, doctors go for a different route, which doesn’t involve working with monoamines such as dopamine. he new route uses another kind of chemical in the brain to facilitate happiness. And that chemical/neurotransmitter is called glutamate, which works off of the NMDA receptor.

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So what ketamine does is that it attaches itself to the NMDA receptors, which target glutamate. This entire process works to elevate the user’s mood.

Typical Candidates for Ketamine Treatment

1. Patients with Treatment-Resistant Depression (TRD)

A patient is considered to have TRD when they've tried two or more antidepressants at adequate doses for adequate durations without significant improvement. These individuals often show the strongest response to ketamine.

2. Individuals Experiencing Suicidal Ideation

Ketamine is one of the few psychiatric treatments that can reduce suicidal thoughts within hours to one day.
Because of this, it's sometimes used in hospitals or specialty clinics as a rapid-acting intervention.

3. Patients with Severe, Debilitating Depression

People whose symptoms severely disrupt: appetite, sleep, functioning, or ability to work may be considered for ketamine when faster relief is needed compared to traditional antidepressants.

4. Some Patients with Bipolar Depression

Ketamine can be used only during depressive phases, not during mania or hypomania.
Careful psychiatric evaluation is required.

Who's Not a Good Candidate

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  • History of psychosis or schizophrenia

  • Uncontrolled hypertension or serious heart disease

  • Active substance use disorder​​​​​

Patients with the following are not good candidates:

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  • Pregnancy or breastfeeding,

  • Minors (except in specialized, rare cases)​​​​​

Ketamine has a lousy reputation for abuse because it’s a powerful drug that can cause addiction if taken in high amounts. But, in minimal doses (that don’t put a person to sleep), it provides rapid relief for depression and leads to profound changes in the symptoms of depression.


If a person has tried the traditional means of treating depression, but nothing has worked, then they might have treatment-resistant depression. Ketamine is a modern mental health treatment to manage that.

How Ketamine Is Administered Today

"New research has also shown that ketamine may provide rapid relief for suicidal thoughts in people with depression."

 

In a recent meta-analysis of clinical studies, ketamine was associated with a significant reduction in suicidal ideation compared to placebo shortly after treatment, with effects seen as early as within one day. Furthermore, repeated dosing seemed to sustain and enhance this effect over time, suggesting that ketamine not only eases depressive symptoms but also helps reduce suicide risk in patients who have not responded to traditional antidepressants.
 

Modern ketamine treatment is performed in controlled medical settings using several established methods.

The three most common are:

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1. Major Depressive Disorder​

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The classic and most researched form.

 

  • Given as a slow 40-minute infusion.

  • Typical dose: 0.5 mg/kg IV, adjustable based on patient response.

  • Patients are monitored throughout for: blood pressure, heart rate, dissociation, and any adverse effects.


This method is widely used for treatment-resistant depression and for the rapid reduction of suicidal ideation.

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2. Intranasal Esketamine (Spravato®) — FDA Approved  

 

 The only ketamine-based treatment officially approved for depression.

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  • Administered in certified clinics using a nasal spray device.

  • Given twice weekly at 56 mg or 84 mg during the initial phase, then tapered.

  • Must be combined with an oral antidepressant.


Patients remain under observation for 2 hours after each dose due to possible: increased blood pressure, dissociation, sedation.


This is the option with the strongest safety regulations and standardized dosing.

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3. Sublingual / Oral Ketamine (Troches or Tablets)

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  • Used in some psychiatric clinics and supervised telemedicine programs.

  • Less predictable absorption compared to IV or intranasal routes.

  • Often used for maintenance after an initial IV series.

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Although effective for some, this route still lacks the extensive clinical evidence of the other two.

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