Stronger early treatment for major depressive disorder after the first medicine fails

AI summary

From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.

The trial is looking for adults with major depressive disorder whose first antidepressant treatment did not work well enough. It compares a six-week intensified drug treatment with usual treatment.

Age

18 to 65 years

Sex

All sexes can join

Disease stage

Major depressive disorder without psychotic features, with moderate symptoms (MADRS score of 20 or more) and trouble in daily life (a score of 5 or higher on any of the three Sheehan Disability Scale scales). The current episode has not responded to treatment (CGI-I of 3 or more).

Earlier treatment

The current treatment failed due to lack of effect. Preferably it was a first-line antidepressant taken for at least 4 weeks in an effective dose. The patient and clinician plan to change treatment. Earlier use of (es)ketamine for depression is not allowed.

Main reasons for not taking part

• Pregnant or breastfeeding
• Used (es)ketamine before for depression
• Known intolerance to (es)ketamine or to all usual-treatment medicines, or a contraindication to them
• Active suicidal thoughts with intent to act, judged unsafe by the clinician
• Current substance use disorder (mild or moderate alcohol or cannabis use disorder and nicotine dependency are allowed)

The registry criteria, word for word

Check if you might fit

Answer for yourself. This is not a decision: only the study team can say whether you can take part.

• Are you between 18 and 65 years old?YesNo

What the trial wants to find out

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.

The 2 groups in the trial

• Major Depressive Disorder EIPT: second-line antidepressant + esketamine nasal sprayTreatment being tested

  Major depressive disorder randomized to EIPT: Switch to second-line antidepressant + esketamine nasal spray or (es)ketamine infusion. Antidepressant: Compound, brand, dosage, frequency and duration up to the investigator's discretion (in accordance with SmPC). Esketamine nasal spray: 2 times per week for 4 weeks. Initial dose 28 mg, after that increases can be made with 28 mg per increase (up to 84 mg per week). This decision is up to the investigator's discretion (in accordance with SmPC). (Es)ketamine infusion: performed twice weekly for 4 weeks. Compound, brand up to the investigator's discretion (in accordance with SmPC).

  Treatment: Esketamine Nasal Product, Ketamine Hydrochloride, and Esketamine hydrochloride

• Major Depressive Disorder TAU: second-line antidepressantExisting treatment, for comparison

  Subject with major depressive disorder, randomized to TAU: switch to second-line antidepressant. When randomized to second-line anti-depressants, this means participants will receive treatment as usual. The physician has the choice to administer any second-line anti-depressant. More specification is not possible, as this is a choice the physician makes with the participant based on the characteristic and preference of the participant (in line with standard clinical practice).

  Treatment: Second-line Antidepressants