claimed that it was too expensive. people who have been already using esketamine were allowed to complete treatment if their doctors considered this necessary. spravato debuted to a cost of treatment of us$32,400 per year when it launched in the united states in march 2019. the institute for clinical and economic review (icer), which evaluates cost effectiveness of drugs analogously to the national institute for health and care excellence (nice) in the united kingdom, declined to recommend esketamine for depression due to its steep cost and modest efficacy, deeming it not sufficiently cost-effective. esketamine is the second drug to be approved for trd by the fda, following olanzapine/fluoxetine (symbyax) in 2009. other agents, like the atypical antipsychotics aripiprazole (abilify) and quetiapine (seroquel), have been approved for use in the adjunctive therapy of mdd in people with a partial response to treatment. in a meta-analysis conducted internally by the fda during its evaluation of esketamine for trd, the fda reported a standardized mean difference (smd) of esketamine for trd of 0.28 using the three phase 3 short-term efficacy trials conducted by janssen. this was similar to an smd of 0.26 for olanzapine/fluoxetine for trd and lower than smds of 0.35 for aripiprazole and 0.40 for quetiapine as adjuncts for mdd. these drugs are less expensive than esketamine and may serve as more affordable alternatives to it for depression with similar effectiveness. adverse effects the most common adverse effects of esketamine for depression (≥5% incidence) include dissociation, dizziness, sedation, nausea, vomiting, vertigo, numbness, anxiety, lethargy, increased blood pressure, and feelings of drunkenness. long-term use of esketamine has been associated with bladder disease. pharmacology pharmacodynamics esketamine is approximately twice as potent an anesthetic as racemic ketamine. in mice, the rapid antidepressant effect of arketamine was greater and lasted longer than that of esketamine. the usefulness of arketamine over esketamine has been supported by other researchers. esketamine inhibits dopamine transporters eight times more than arketamine. this increases dopamine activity in the brain. at doses causing the same intensity of effects, esketamine is generally considered to be more pleasant by patients. patients also generally recover mental function more quickly after being treated with pure esketamine, which may be a result of the fact that it is cleared from their system more quickly. this is however in contradiction with arketamine being devoid of psychotomimetic side effects. unlike arketamine, esketamine does not bind significantly to sigma receptors. esketamine increases glucose metabolism in the frontal cortex, while arketamine decreases glucose metabolism in the brain. this difference may be responsible for the fact that esketamine generally has a more dissociative or hallucinogenic effect while arketamine is reportedly more relaxing. however, another study found no difference between racemic ketamine and esketamine on the patient's level of vigilance. interpretation of this finding is complicated by the fact that racemic ketamine is 50% esketamine. pharmacokinetics esketamine is eliminated from the human body more quickly than arketamine (r(–)-ketamine) or racemic ketamine, although arketamine slows the elimination of esketamine. history esketamine was introduced for medical use as an anesthetic in germany in 1997, and was subsequently marketed in other countries. in addition to its anesthetic effects, the medication showed properties of being a rapid-acting antidepressant, and was subsequently investigated for use as such. esketamine received a breakthrough designation from the fda for treatment-resistant depression (trd) in 2013 and major depressive disorder (mdd) with accompanying suicidal ideation in 2016. in november 2017, it completed phase iii clinical trials for treatment-resistant depression in the united states. johnson & johnson filed a food and drug administration (fda) new drug application (nda) for approval on 4 september 2018; the application was endorsed by an fda advisory panel on 12 february 2019, and on 5 march 2019, the fda approved esketamine, in conjunction with an oral antidepressant, for the treatment of depression in adults. in august 2020, it was approved by the u.s. food and drug administration (fda) with the added indication for the short-term treatment of suicidal thoughts. since the 1980s, closely associated ketamine has been used as a club drug also known as "special k" for its trip-inducing side effects. society and culture names esketamine is the generic name of the drug and its inn and ban, while esketamine hydrochloride is its banm. it is also known as s(+)-ketamine, (s)-ketamine, or (–)-ketamine ((-) ketamine) as well as by its developmental code name jnj-54135419. esketamine is sold under the brand name spravato for use as an antidepressant and the brand names eskesia, ketanest, ketanest s, ketanest-s, keta-s for use as an anesthetic (veterinary), among others. availability esketamine is marketed as an antidepressant in the united states; and as an anesthetic in the european union. legal status esketamine is a schedule iii controlled substance in the united states.