Products
Esketamine nasal spray was approved in the US and EU in 2019 and in many countries in 2020 (Spravato).
Structure and properties
–Ketamine is the pure -enantiomer of ketamine (C13H16ClNO, Mr = 237.7 g/mol). The racemate ketamine is a cyclohexanone derivative derived from phencyclidine (“angel dust”). It is a ketone and an amine and is present in the nasal spray as esketamine hydrochloride, a white crystalline powder that is readily soluble in water.
Effects
Esketamine (ATC N06AX27) has antidepressant properties. Unlike traditional antidepressants, it has a rapid onset of action in the range of hours and a different mechanism of action. The effects are based on non-selective and non-competitive antagonism at -methyl-D-aspartate (NMDA) receptors. This results in a transient increase in glutamate release. In addition, numerous other interactions with other receptor systems have been described. Esketamine has a higher affinity for the NMDA receptor than the -enantiomer. The half-life is in the range of 7 to 12 hours.
Indications
In combination with an SSRI or SNRI for the treatment of treatment-resistant major depression.
Dosage
According to the SmPC. The drug is administered intranasally and absorbed into the bloodstream through the nasal mucosa. This avoids parenteral administration, reduces the dose, and circumvents the problem of low oral bioavailability. Therapy takes place under the supervision of a healthcare professional. Nothing should be eaten at least two hours before treatment and nothing should be drunk 30 minutes before, because nausea and vomiting may occur as adverse effects.
Abuse
Ketamine and esketamine are abused as intoxicants.
Contraindications
- Hypersensitivity
- Patients for whom an increase in blood pressure or intracranial pressure poses a serious risk.
For complete precautions, see the drug label.
Interactions
Drug-drug interactions have been described with centrally depressant drugs, stimulants, and agents that increase blood pressure. Esketamine is a substrate of CYP450 isoenzymes, particularly CYP2B6 and CYP3A4.
Adverse effects
The most common potential adverse effects include dizziness, nausea, dissociation, headache, drowsiness, vertigo, taste disturbance, hypesthesia, and vomiting.