A randomized single-blinded prospective study to evaluate the efficacy of an individualized supervised 8-week exercise program in subjects with moderate to severe depressive episodes compared to treatment-as-usual

The purpose of this study is to assess the efficacy of a supervised and indvidualized 8-week exercise program compared to treatment-as-usual in subjects with a moderate or severe depressive episode in the context of unipolar depression or bipolar affective disorders. Numerous previous studies suggest that exercise may help to improve the symptoms of depression. Moreover, exercise was shown to enhance neuroplasticity in adults whereas depression results in decreased neuroplasticity. Here, we aim at elucidating whether a newly developed supervised, Internet-based, individualized exercise program of the Institute of Sports Science and the Department of Psychiatry and Psychotherapy at the University Mainz is more effective in reducing depressive symptoms than treatment-as-usual. Furthermore, this study will clarify if severely depressed subjects are able to adhere to an internet-based exercise therapy.

Inclusion Criteria:

1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local subject privacy regulations.
2. Aged 18 to 65 years old, inclusive, at the time of informed consent.
3. Montral Cognitive Assessment (MoCA) > 26 to exclude cognitive impairment.
4. Apart from a clinical diagnosis of major depression or bipolar affective disorder, the subject must be in good health as determined by the Investigator, based on medical history and physical examination.
5. QIDS scores > 5

Exclusion Criteria:

1. Use of antidepressive medications or benzodiazepines at doses that have not been stable for at least 6 weeks prior to Screening

2. Psychotherapy that started less than 8 weeks prior to Screening

3. Any clinically significant psychiatric illness other than major depression or bipolar affective disorder

4. Transient ischemic attack or stroke or any unexplained loss of consciousness within 1 year prior to Screening

5. Any uncontrolled medical or neurological/neurodegenerative condition that, in the opinion of the Investigator, might impair treatment compliance and adherence

6. History of unstable angina, myocardial infarction, chronic heart failure (New York Heart Association Class III or IV), or clinically significant conduction abnormalities (e.g., unstable atrial fibrillation) within 1 year prior to Screening

7. Clinically significant 12-lead ECG abnormalities, as determined by the Investigator

8. Uncontrolled hypertension defined as: average of 3 systolic blood pressure [SBP]/diastolic blood pressure [DBP] readings > 165/100 mmHg at Screening

9. History of malignancy or carcinoma, with the following exceptions:

   i) Subjects with cancers in remission more than 5 years prior to Screening. ii) Subjects with a history of excised or treated basal cell or squamous carcinoma. iii) Subjects with prostate cancer in situ.

10. History of seizure within 2 years prior to Screening.

11. Recent history (within 1 year of Screening) of alcohol or substance abuse as determined by the Investigator, a positive urine drug (due to non-prescription drug) or alcohol test at Screening

12. Clinically significant systemic illness or serious infection (e.g., pneumonia, septicemia) within 30 days prior to or during Screening

13. History of human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV)

14. Any other medical conditions (e.g., renal disease) that are not stable or controlled, or, which in the opinion of the Investigator, could affect the subject's safety or interfere with the study assessments

15. Female subjects who are pregnant or currently breastfeeding

16. Participation in another study

17. Other unspecified reasons that, in the opinion of the Investigator or Biogen, make the subject unsuitable for enrollment