This parallel, randomised, controlled trial (n=418) will investigate the effect of a six-week ketamine for Major Depressive Disorder (MDD) compared to treatment as usual in subjects who had a first-time treatment failure on their first-line treatment.
Led by Dr. Inge Winter, UMC Utrecht, the study aims to address the significant distress and impairment caused by MDD, a common psychiatric illness affecting over 28 million people in the European Union. Currently, antidepressant medication is prescribed through a trial-and-error process, with esketamine nasal spray recently approved for patients with treatment-resistant MDD (TRD).
The trial will compare early-intensified pharmacological treatment to standard treatment, with primary outcomes measured through the Montgomery-Åsberg Depression Rating Scale (MADRS) at six weeks.
Secondary outcomes include changes in severity and improvement in global functioning, levels of depression and anxiety, cognitive performance, quality of life, and side effects.
Participants, aged 18 to 65, diagnosed with MDD without psychotic features, and experiencing their first treatment failure, will be enrolled. The study will be conducted across multiple centres in Austria, Germany, Italy, Spain, and the United Kingdom, with a projected start date of March 31, 2024, and an estimated completion date of June 30, 2026.
Trial Details
Over 28 million people suffer from current depressive disorder in the European Union. Major depressive disorder (MDD) is one of the most common psychiatric illnesses. The symptoms cause clinically significant distress or impairment in social, occupational, and other important areas of functioning. To treat MDD, there are several antidepressants available and prescribing medication is a process of trial-and-error. Guidelines do not explicitly advise on the order in which antidepressant medication should be prescribed. The choice of antidepressant should be tailored to the patient, while involving the patient in the decision-making process. In general, the choice for the first- and second-line treatment will be a second-generation antidepressant. Recently, esketamine nasal spray (intranasal (IN) administration) was approved for patients with treatment-resistant MDD (TRD). A patient is diagnosed with TRD when having used two antidepressants in sufficient duration and adequate dose without sufficient effect. TRD is associated with a negative impact on quality of life, higher risk for hospitalisations and suicide, comorbidities, poorer social and occupational functioning and a high carer burden. The efficacy of intranasal use of esketamine has been demonstrated in MDD subjects with treatment-resistant symptoms but also in subjects with non-treatment resistant depression, and is approved by the FDA and EMA as a third-line treatment. Besides the registered esketamine nasal spray, which is not available in all countries to all patients because of the high costs, off-label utilization of (es)ketamine infusions (IV) is growing extensively over time to treat TRD. Research conducted so far indicates an unequivocal initial substantial response to (es)ketamine IV in MDD populations, regardless of whether or not patients suffer from treatment resistant MDD. However, until now, there has not been a study investigating this in a sufficiently large population. This may be a unique opportunity to potentially prevent patients progressing into a treatment resistant illness stage. The potential implications of the results of the current study are the prevention of unnecessary trials of ineffective treatments, reducing subject burden substantially, as well as a reduction of healthcare and societal costs.NCT Number NCT05973851
Sponsors & Collaborators
Utrecht UniversitySome researchers at Utrecht University are working on a large psychedelics study with colleagues from Leiden University, but this university hasn't set up any department specifically for psychedelic studies.