Recent research in mice models of Alzheimer's disease (AD) has demonstrated that one hour per day of exposure to 40 Hz flickering light therapy can halt the disease's progression, and improve cognition and memory. Moreover, recent data suggest that 40 Hz light stimulation may induce neuroplasticity and reduce neuroinflammation.

In this study, the investigators aim to evaluate the antidepressant effects of 40 Hz light stimulation in Major Depressive Disorder (MDD). Patients will be exposed to 40 Hz invisible spectral flickering light (active setting) or continuous non-flickering white light (sham setting) in a home setting for 1 hour each day.

Major depression is a major societal challenge worldwide and a substantial proportion of patients do not attain remission. Major depressive disorder (MDD) bears several key neurobiological similarities with Alzheimer's Disease, namely cognitive deficits, impaired neuroplasticity, neurodegeneration, and neuroinflammation. Inducing neuroplasticity and reducing neuroinflammation are thought to be key cellular targets in the treatment of MDD. However, 40 Hz light stimulation research in the context of MDD is limited.

In this double-blinded, randomized placebo-controlled trial the primary objective is to investigate the antidepressant effect of a non-invasive neurostimulation therapy using a 40 Hz masked flickering light. This study utilizes a novel way of masking light by alternating the spectral composition of white light, resulting in the flicker unnoticeable to human perception.

The primary outcome measure of this study is the estimated difference in the Hamilton Depression Rating sub-scale (HAM-D6) scores between groups at week 6. Furthermore, investigators want to assess whether 40 Hz masked flickering light therapy produces a similar early shift in neural and cognitive response to emotional information seen with antidepressant therapy and whether this predicts treatment efficacy. Suicidal ideation, sleep patterns, and quality of life will be also investigated in order to evaluate the 40 Hz masked flickering light stimulation effects on other symptoms of depression. Explorative analysis of the EEG data will be performed from baseline to week 6 for the further development and validation of EEG-based biomarkers.

A total of 60 participants will be enrolled for a six weeks treatment period followed by a two weeks follow-up period. Participants will be recruited from a psychotherapeutic outpatient unit. Medication should be unchanged for the last 4 weeks and during the study period.

Inclusion Criteria:

1. Subjects between 18 and 75 years of age.
2. Subjects with a diagnosis of major depressive episode and currently experiencing a depressive episode according to DSM-5
3. Subjects with an MDI score > 21 at screening
4. Subjects on stable medication and/or psychotherapy for at least 4 weeks before starting the trial.
5. Subjects, who are willing to comply with the scheduled plan and are able to use the device for 1 hour per day for 6 weeks.
6. Subjects who can understand the oral and written study information and willing to sign an informed consent.

Exclusion Criteria:

1. Subjects with a history of photosensitive migraines and/or epileptic seizures
2. Subjects with a known eye disorder that might be sensitive to light treatment.
3. Subjects with a known history of bipolar disorder according to DSM-5 criteria
4. Subjects with suicidal ideation corresponding to a score of 2 or more on the HAM-D 17 scale item 3 or if the patient or investigator is uncertain of the degree of suicidal risk
5. Subjects with current psychotic symptoms. However, subjects with a prior psychotic depression or subjects with an actual psychotic depression episode that at the time of informed consent no longer fulfills the psychosis criteria are allowed to participate.
6. Subjects with current drug or alcohol dependence based on their medical records or the M.I.N.I. interview.
7. Subjects with a known history of borderline personality disorder
8. Subjects currently enrolled in another investigational treatment study.
9. Subjects with progressive neurodegenerative or neoplastic disease.
10. Subjects who are unable to understand the study procedures or handling of the NSS device.
11. Subjects who are pregnant at the time of inclusion or unsafe contraception in women of fertile age