A form of ketamine called esketamine could soon be licensed for use in patients with treatment-resistant depression.
Pharmaceutical company Janssen has submitted an application for marketing authorisation of its esketamine nasal spray in Europe, for use in patients who have not responded to two different antidepressant treatments.
It comes as NICE is currently in the early stages of looking at esketamine for treatment-resistant depression. It will assess the clinical and cost effectiveness of the drug within its marketing authorisation for the treatment of major depressive disorder.
But researchers questioned the introduction of this treatment as a third-line option, warning it could be ‘extremely disruptive’ and calling for a ‘precautionary approach’.
Esketamine is part of the ketamine molecule, but does not act in the exact same way as ketamine.
The nasal spray belongs to a potential new class of rapidly-acting antidepressants known as glutamate receptor molecules, which are thought to help restore synaptic connections in the brain of people with treatment-resistant depression.
The new licence application, which was submitted to the European Medicines Agency last week, would allow patients to self-administer the treatment, under the guidance of a doctor, if approved.
Janssen based its application on five phase three trials of the drug: three short-term studies, one randomised withdrawal and maintenance of effect study, and one long-term safety study.
According to the company, data from these studies demonstrated that treatment with esketamine nasal spray plus a newly initiated oral antidepressant, was associated with a rapid reduction of depressive symptoms, as early as day two, and reduced the risk of relapse by 51% in stable remitters.
The long-term safety study showed that the esketamine nasal spray doses were generally tolerated, Janssen added.
But despite the positive view from the company, the two most recent clinical trials failed to meet their primary endpoints, with the latest one failing to show that esketamine was more effective at reducing the severity of depression than an oral antidepressant plus placebo nasal spray.
Researchers also raised concerns over the issues of dependence, and whether esketamine should come as early as the third option in the treatment pathway.
University of Oxford associate Professor Rupert McShane, who has been looking at ketamine as a potential treatment for clinical depression said: ‘The Janssen trials in esketamine have been in people who are resistant to only two antidepressants, the scope is really looking at whether this can be a third-line treatment.’
But Professor McShane, who also sits on the Janssen advisory board, stressed that the implications of the treatment must be addressed.
He said: ‘That is really the main issue, because it would be extremely disruptive for current psychiatric practice where other sorts of avenues are explored first, so there is really a question over where it should be pitched in the pathway.’
He explained that ‘dependence is a key issue that needs to be addressed at a public policy level’ and said ‘we need to take a precautionary approach on this, we need to not let the genie get out of the bottle’.
‘The implication of this is that you could be in a position where someone does not respond to two SSRIs in primary care, is referred to secondary care and the next drug they are given is esketamine,’ he warned.
A spokesperson for Janssen said: ‘If approved, esketamine nasal spray would be administered under the care and observation of a healthcare professional and several measures will be in place to help ensure the safe and appropriate use of esketamine nasal spray.
‘Janssen is committed to developing esketamine nasal spray for treatment-resistant depression; a serious biological illness with high unmet need.’
Researchers have been looking at ketamine as a treatment for severe depression for years, with previous studies showing that the drug could halve depression scores in some patients who had previously been resistant to treatments.