Ketamine: What You Need to Know

Anyone following psychiatry in the media will have heard about ketamine. Ketamine as a medicine was primarily used for starting and maintaining anesthesia. It’s also a well-known recreational drug (special K) for its hallucinogenic and dissociative effects. Ketamine nasal spray was approved by the Food and Drug Administration (FDA) in March of 2019 for treatment resistant depression (TRD). Ketamine intravenous infusions were being offered for several years prior to FDA approval as an off-label treatment for TRD. esketamine is the S-isomer of ketamine (usually a mixture of both s-ketamine and r-ketamine). The nasal spray device contains 28 mg of esketamine and is administered as a single spray in each nostril.

The guidelines for dosing the medication include an induction phase (weeks 1-4) of 56 mg on day one followed by 56 mg or 84 mg twice per week. From week five on 56 mg or 84 mg will be given every 1-2 weeks depending on patient response. Patients are required to remain in the office to be observed by a healthcare provider for at least two hours after receiving the medication. The device cannot be taken home, and the patient must come to the office for each dose. The clinic must be a certified Spravato treatment center to use the medication. Patients should be remined to avoid food 2 hours prior to treatment, and liquids 30 minutes prior to treatment. Blood pressure should be monitored 40 minutes after the dose. 

Some of the limitations associated with this medication include high cost to the patient. Insurance will cover some of the cost and Johnson & Johnson set a list price of $590 to $885 per treatment. The major side effects include sedation, dissociation, increased blood pressure which is transient, cognitive impairment and inability to drive. One of the major arguments against the use of ketamine products is the potential for abuse/misuse. Some of this is mitigated by only allowing the medication to be administered at certified centers, and not allowing take home doses. Still patients with a history of substance use disorder may be at risk, and each case should be evaluated carefully. 

What makes esketamine so exciting is this is the first medication that works through a different mechanism of action (MOA) to treat depression. The focus of depression treatment to this point has been on monoamines such as serotonin. Esketamine acts as N-methyl-D-aspartate receptor antagonist (NMDAR). The other exciting finding is the rapid relief of depressive symptoms this medication provides. Efficacy can be seen as early as 24 hours after the first dose. There is no other antidepressant medication on the market that can produce improvements in depressive symptoms so rapidly.  

Esketamine’s use remains limitted to patients with treatment resistant depression. Research indicates it’s moderately effective and should be offered as an alternative for those who prefer medication over electroconvulsive therapy (ECT). The barriers to use include high cost, frequent clinic visits, and lots or regulation and monitoring requirements on the part of clinics offering the treatment.

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