Spravato for Treatment Resistant Depression

Treatment resistant depression (TRD) is defined as depression that fails to respond to 2 or more medications at adequate dose and duration.  Unfortunately, many patients with depression fall into this TRD category.  Studies show that about 1 out of every 3 depressed patients meets or will meet criteria for TRD.

When someone comes in to seek help for depression, they usually go through a step wise progression of different treatment options.  Starting with psychotherapy and/or medications and progressing to electroconvulsive therapy (ECT) in the most severe cases.  Medication management is still by far the most common form of depression treatment.

Depression treatment ladder:

Spravato is a form of ketamine and a category III controlled substance, it is the most recent medication to get FDA approval for the treatment of TRD.  Spravato is different than most traditional antidepressants because its mechanism of action is unique, as opposed to that used by most depression medication which is primarily modulating serotonin levels.  We do not fully understand how Spravato causes its antidepressant effect, but we do know it works primarily as a NMDA (N-methyl-D-aspartate) receptor antagonist.  This results in glutaminergic neuron activity, which can be understood as modulating the neurons that turn things on in the brain.

One of the most interesting characteristics of Spravato is that most patients who respond to the medication felt the antidepressant effect quickly, in some cases as little as 24-48 hours post first treatment dose.  This is different than that for most traditional antidepressants that require several weeks of treatment before one starts to receive benefit.

Spravato comes in the form of a nasal spray, it is not a medication that one takes at home like most other meds.  It is used in the doctor's office (called a Spravato treatment center) and patients can only obtain it at a Spravato treatment center.  Spravato is self-administered by patients under the supervision of a clinician, the administration takes about 15 minutes and there is a required monitoring period of 2 hours post administration.  Patients need to be aware that they will need to be at the treatment center for the full duration of this time.  It is usually used twice a week for the first month, then once a week for the second month with switching to as clinically needed thereafter.  Most patients should plan for at least 3 months of treatment, yet one needs to be aware than many patients require long term treatment.

Regarding side effects, by far the most common are sedation and dissociation (described by most of our patients as being high).  Additionally, there can be a temporary increase in blood pressure, headaches, dizziness and gastro-intestinal symptoms amongst others.  These symptoms should be mostly resolved by the time patients are ready to leave the treatment center.  Patients must also be aware that they will not be able to drive themselves home and that they will need to arrange transportation, but can go back to driving the day after treatment.

If you are interested in more information, please visit the following:

Spravato official website

MindfulBH Spravato website

TRD can be hard to treat, but now patients and doctors have a new safe and effective treatment option.  It is important to remember that depression is a chronic condition that can get better with treatment.


Ivan E. Cichowicz, MD DABPN Dr. Cichowsicz is the Medical Director of Mindful Behavioral Health and he specializes in the treatment of treatment resistant depression.

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