Vassilis N. Panagopoulos, MD
Ketamine is a classic anesthetic medication, which comprises of two racemic enantiomers (2 molecules that are mirror images of each other): S-ketamine (esketamine) and R-ketamine.
Esketamine is the active ingredient of Spravato, a medication approved for the treatment of treatment-resistant depression. Treatment-resistant depression is typically defined as major depressive disorder not responding to at least 2 adequate trials of conventional antidepressants.
The effects of these medications to the NMDA receptors in the brain are likely involved in their mechanism of action.
Esketamine is administered intranasally, i.e. as a nasal spray. It is not administered by injection which is an advantage over treatment with ketamine (which is typically administered intravenously).
Esketamine appears to be binding to the NMDA receptors in the brain more potently than R-ketamine. This may allow for a lower dose to be used to achieve a robust antidepressant effect with possibly fewer side effects in comparison to ketamine (the mixture of esketamine and R-ketamine).
Large clinical trials have shown that esketamine has similar effects on depression to ketamine. The data that supports the clinical use of esketamine is of higher quality and longer duration than that of ketamine. Namely, it appears to induce remission of depression (absence of significant symptoms) approximately 10 times more frequently than trying a different antidepressant medication in patients with treatment-resistant depression. Also, it appears that treatment with esketamine may be safer in comparison to ketamine, likely due to the safer method of administration (intranasal versus intravenous). Some cognitive side effects may be less frequent with esketamine.
Furthermore, esketamine has been officially approved for the treatment of treatment-resistant depression by the FDA and the European Medicines Agency whereas ketamine has not. Ketamine is used clinically for this indication “off-label”, which means that it has not received approval by the regulatory bodies (in spite of expanding positive scientific data).
Esketamine can cause side effects including sleepiness, dizziness, dissociation (feeling disconnected from one’s thoughts or emotions), hallucinations, confusion, abuse/addiction, nausea/vomiting, increased blood pressure, respiratory depression. The risk for side effects is mitigated by closely observing the patient and actively monitoring for side effects.
No, sustained abstinence from any and all substances of abuse (except nicotine/tobacco) is required in order to receive treatment with esketamine. Urine drug screen testing may be required to ensure the safety of the treatment at any point.
Conventional antidepressants (such as SSRIs or SNRIs) are typically continued during esketamine treatment. Some medications used for anxiety, namely benzodiazepines, may have to be discontinued as there is some evidence suggesting that they may interfere with the effectiveness of the treatment. In addition, discontinuing benzodiazepines increases the safety margin of esketamine treatment. Active participation in psychotherapy is strongly encouraged concurrently as its effects are complementary to those of pharmacologic treatments.
Dr. Panagopoulos, a US-trained psychiatrist with expertise in multiple interventional psychiatric treatments, runs an esketamine outpatient clinic at his private practice in Limassol. The first step to treatment is to complete a comprehensive intake evaluation with Dr. Panagopoulos. This is crucial in order to reach an accurate diagnosis and review the treatment history of each individual patient thoroughly. Medical testing may also be required depending on the age and the presence of any co-occuring medical conditions. If it is deemed that esketamine is medically indicated in the absence of any contraindications, treatment can be initiated. The administration is typically completed under strict medical supervision at our medical office so that any potential side effects that may arise can be addressed promptly. Following careful selection of patients and under close supervision, this medication can be administered safely and provide significant relief to patients with severe clinical depression.
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