Treatment-resistant depression is an emerging area of research as some patients can cycle through many different antidepressants with little or no therapeutic effect. Over time, it becomes harder to achieve clinical remission, and Spravato is a novel agent which aims to fill this therapeutic gap.
Spravato contains esketamine, one of the S-enantiomers of ketamine, which is indicated for moderate to severe major depressive disorder in adults who have tried two or more antidepressants. It is intended to be combined with an SNRI or SSRI.
Esketamine is a NMDA receptor modulator which is given at a lower antidepressant dose than what is needed to achieve anaesthetic activity. Note that esketamine is a controlled substance which has a potential for abuse. Hence, prescribers, patients and pharmacists must be enrolled in the Janssen Journey Program to get access to Spravato.
Spravato is given as a nasal spray in each nostril. In the induction phase (Weeks 1 to 4), patients are dosed twice weekly. The first dose is given as 28 mg or 56 mg. Subsequent doses can range between 28 mg, 56 mg or 84 mg. In the maintenance phase, patients are dosed once weekly from Weeks 5 to 8. Finally, from Week 9 onwards, there is an option to dose patients every one to two weeks.
The Spravato device contains 28 mg in total, given as 1 spray in each nostril. Hence, multiple devices may be required, with a 5 minute interval between devices. No priming is required.
Spravato has the potential to cause many adverse effects as follows:
Cardiovascular: caution in those with cardiovascular disorders: any blood pressure over 140/90 is considered uncontrolled and it should not be administered. Spravato can cause a spike in blood pressure, with maximum effect 40 minutes post dose and lasting up to 4 hours.
Psychiatric: Patients should be monitored for dissociation, euphoria, hallucinations ,sedation and respiratory depression for at least 2 hours. Patients should avoid operating heavy machinery until they have had a full night of sleep.
Other: Urinary tract symptoms (UTI, frequency)
-No food 2 hours before the dose and no drink 30 minutes before the dose (due to risk of nausea and vomiting) -No alcohol 24 hours before the dose -No intranasal corticosteroid or decongestant 1 hour before the dose
-Potential for sedation: benzodiazepines, alcohol, opioids -Potential for hypertensive crisis: amphetamines, triptans, pseudoephedrine, MAO-inhibitors