Following the EU, Switzerland has also recently approved a nasal spray based on the active ingredient ketamine, which is known as a party drug. The preparation can be used as an add-on in case of therapy resistance.
The drug Spravato® (esketamine) is approved in combination with an SSRI (selective serotonin reuptake inhibitor) or SNRI (selective norepinephrine reuptake inhibitor) for adults with treatment-resistant major depression [1]. Treatment resistance is defined as a lack of response to at least two different antidepressants [2]. The approval is based on five phase III studies: three short-term studies, one long-term safety study, and one randomized relapse prevention study [2].
Very rapid onset of action
The great advantage of esketamine is that it acts comparatively quickly. In pivotal trials, more than 1600 patients over the age of 18 years with treatment-resistant depression received esketamine nasal spray combined with a newly administered oral antidepressant [2]. In the short-term studies, a clinically significant response was measurable in the verum group up to 28 days after baseline. Response was defined as a reduction in total Montgomery-Asberg Depression Rating Scale (MADRS) score of at least 50% from baseline in the induction phase. In the multicenter, randomized, double-blind, active-controlled, long-term relapse prevention trial, esketamine nasal spray combined with an antidepressant reduced the risk of relapse by 70% in patients with stable response compared with the placebo group. In patients in stable remission, the risk of recurrence decreased by 51%. The long-term safety study found that even with up to 52 weeks of therapy, esketamine nasal was generally well tolerated.
The antidepressant effect probably occurs via antagonism at the NMDA receptor. This provides a transient increase in glutamate release that leads to increased stimulation of the AMPA receptor and subsequently increased neurotrophin-induced signal transduction, which may contribute to restored synaptic function in brain regions responsible for mood and emotion regulation [3].
Blood pressure control recommended
The nasal spray is a single-use applicator containing a total of 28 mg of esketamine divided into two sprays (one spray per nostril). The nasal spray is intended for use by the patient himself/herself under the supervision of healthcare professionals, according to the respective dosage recommendations. Before using the nasal spray, the patient’s blood pressure must be measured. If baseline blood pressure is elevated, the risks associated with short-term elevated blood pressure levels must be weighed against the benefits of treatment. The spray must not be used if increased blood pressure or increased intracranial pressure poses a serious risk. Blood pressure should be checked approximately 40 minutes after application of Spravato® and again thereafter at clinical discretion [3].
Source: Janssen-Cilag International
Literature:
- Mahase E: Esketamine is approved in Europe for treating resistant major depressive disorder. BMJ 2019; 367: l7069.
- European Medicines Agency. Esketamine nasal spray Summary of Product Characteristics, www.ema.europa.eu/en/medicines
- Siebenand S: Esketamine nasal spray approved for depression. Pharmaceutical Journal, Dec. 23, 2019, www.pharmazeutische-zeitung.de
- Swissmedics: Spravato®, nasal spray (esketaminum), www.swissmedic.ch
HAUSARZT PRAXIS 2020; 15(4): 27
