Emerging treatments

Esketamine nasal spray

In March 2019, the Food and Drug Administration approved esketamine nasal spray, to be used in conjunction with an oral antidepressant, for treatment-resistant depression in adults. Administration of the drug is only available through a restricted distribution system, under a risk evaluation and mitigation strategy (REMS) in which both the prescriber and patient sign a patient enrollment form. The drug must be self-administered by the patient, who is supervised by a healthcare provider in a certified medical office, and the patient must be monitored for at least 2 hours because of the risk of sedation; difficulty with attention, judgment, and thinking (dissociation); suicidal thoughts and behaviors; and the potential for drug misuse. Be aware that patients with poorly controlled hypertension or pre-existing aneurysmal vascular disorders may be at increased risk for adverse cardiovascular or cerebrovascular effects. The efficacy of esketamine was evaluated in three short-term (4-week) clinical trials and one longer-term maintenance-of-effect trial.[214][215][216][217][218]​​ In one of the short-term studies, esketamine nasal spray demonstrated statistically significant effect compared with placebo on the severity of depression, and some effect was seen within 2 days. The two other short-term trials did not show statistically significant effectiveness. In the longer-term maintenance-of-effect trial, esketamine plus an oral antidepressant resulted in a statistically significantly longer time to relapse of depressive symptoms compared with placebo nasal spray plus an oral antidepressant. The most common side effects were disassociation, dizziness, nausea, sedation, vertigo, decreased feeling or sensitivity (hypoesthesia), anxiety, lethargy, increased blood pressure, vomiting, and feeling drunk. The European Medicines Agency has also approved esketamine nasal spray, to be used in conjunction with a selective-serotonin reuptake inhibitor or a serotonin-norepinephrine reuptake inhibitor, for treatment-resistant major depression disorder in adults who have not responded to at least two different antidepressants in the current moderate to severe depressive episode.

Nonpharmacologic interventions

Other potentially effective interventions for ongoing suicidal ideation include online and mobile telephone applications and formal physical exercise programs.[219][220][221]

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