A nasal spray for depression? It doesn’t pass the sniff test just yet

A nasal spray can ‘rapidly and significantly’ improve the symptoms of depression in patients who do not respond to other therapies, according to a study published in the journal Biological Psychiatry.

During the double-blind study, by the pharmaceutical company Janssen, researchers examined the safety and efficacy of esketamine (which is a component of the general anaesthetic ketamine) in patients with treatment-resistant depression.

They randomly assigned 30 patients to receive either a placebo, or a dose (either 0.2mg or 0.4mg) of esketamine. The earliest onset of an antidepressant effect was measured two hours after the first dose. Within three days, over 60 per cent of patients receiving esketamine noticed an improvement in depressive symptoms, whereas none of the patients in the placebo group responded.

Seventeen per cent of patients taking the higher dose experienced a change immediately after taking the drug, which subsided within four hours.

Murray Stein, the deputy editor of the journal that published the research, said: ‘The study shows clear benefits of the drug over placebo and suggests that the lowest of the two doses may be equally efficacious but also safer.

‘Though the mechanism of ketamine (and esketamine) antidepressant effects remains unclear, this study clearly demonstrates a benefit, at least in the short term, of this drug for treatment-resistant depression.’

The company is currently carrying out clinical trials to test a wider range of doses, assess the side effects, and establish the long-term safety of esketamine.

Instant analysis
The generalisability of this study may be limited by a number of factors, including the low numbers of patients (30) and the applicability of the original trial (based on intravenous administration of esketamine) to the use of a nasal spray to deliver the drug. Side effects included headache, nausea and dissociation.

Nevertheless, depression is a condition associated with major morbidity and associated mortality, and it is encouraging to see novel therapeutic developments in this area.

Depression is likely to involve various stressors in the patient’s life, and effective therapies often rely on approaches other than, or complementary to, pharmacological treatments. It remains to be seen if a rapidly acting spray could be considered a useful adjunct to more conventional therapeutic approaches.

It should be pointed out that the authors of the original study declare themselves to be employees and shareholders of a major pharmaceutical company.
JCH
Research score: 2/5