Major depressive episode (MDE) are severe and common psychiatric disorders that affect up to 20% of the general population. MDE cause a decrease in psychosocial functioning, quality of life, and is associated with a high rate of suicides. They will be the leading cause of disability by 2030 according to the World Health Organization. The international effort carried out to identify biomarkers of MDE has been hampered by the heterogenous nature of MDE (unipolar, bipolar, seasonal, non-seasonal) and their heterogeneous response to treatment. Response rate to antidepressant drugs is only 40 to 50%, leading to the use of drug combinations and development of alternative therapeutics such as light therapy (LT). It was demonstrated that LT, as a first line treatment of MDE with and without seasonal pattern (± SP), has comparable efficacy to antidepressants. LT has the advantage of being also effective in improving both sleep, alertness and circadian rhythms, which may be altered in depression, contrary to antidepressant drugs that target mainly mood. Further research is warranted to determine the most efficient lighting parameters to use depending on depression characteristics, as well as to identify signature biomarkers of response. Besides, no studies have directly evaluated both subjective and objective biomarkers of sleep, wake, biological rhythms, and light signalling pathways and activation in patients with MDE ± SP. The main objective of the research will be to identify the signature of response to LT examining the correlation between the measures of biological and clinical parameters before LT and their evolution at the end of the procedure, and the therapeutic response.
The primary endpoint of the study will be the therapeutic response to LT measured by the difference of MADRS score between Visit 1 and Visit 4 (end of the therapeutic protocol). Therapeutic response to LT considered as a success will be defined as at least a 50% reduction of MADRS score between the two visits.
Adults between 18 and 65 years old
Patients with a diagnosis of MDE as part of a unipolar or bipolar disorder (DSM-5 TR criteria)
Patients with a clinician-rated MADRS score ≥ 20 indicating a moderate to severe depressive symptoms with a prescription of LT for MDE treatment
For Lithium, controlled by serum lithium level, >0.5 mEq/L for Téralithe 250 and > 0.7 mEq/L for Téralithe LP 400 ; for Sodium Valproate, controlled by serum sodium divalproate level >40mg/L
Patients with a DSM-5 diagnosis of schizophrenia, suffering from paranoid or delusional disorders, any other psychotic features or other nonstabilized mental disorders
Patients with other antidepressant strategies than LT or mood stabiliser initiated in the month prior to inclusion
Patients with a therapeutic resistance of current MDE (lack of response to ≥2 antidepressants of 2 different classes at therapeutic doses for >6 weeks)
Patients with a LT used in the last 1 month
Single group
Light therapy
DeviceIt consists of daily exposure to 10 000-lux fluorescent white light box (French light box, Dayvia®, Slim style device) for 30 minutes. Patients with a diagnosis of major depressive episode (MDE) will be treated for 4 weeks by light therapy in the morning after awakening, preferably between 7 and 9 am. Patients with bipolar depression and medicated will need to be pre-treated with a mood stabiliser antimanic agent to limit the risk of manic switch. In case of treatment-emergent hypomanic symptoms assessed with the YMRS for all patients, the exposition to LT will be reduced to 15 min or stopped if the patient is already at 15 min. In case of LT cessation for hypomanic switch, the patient will be considered as responder.
Therapeutic response to luminotherapy measured by the difference of Montgomery-Asberg Depression Rating Scale (MADRS) score between Visit 1 (inclusion) and Visit 4 (5 weeks)
Measurement of the depression severity score obtained from the Montgomery-Asberg Depression Rating Scale (MADRS) questionnaire before and after light therapy treatment. Score range (min - max): 0-60. Higher score relates to worse depression severity.
Change in depressive symptoms from baseline to post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of the depressive severity score obtained from the Montgomery-Asberg Depression Rating Scale (MADRS) questionnaire before, during and after light therapy treatment. Score range (min - max): 0-60. Higher score relates to worse depression severity.
Change in manic symptoms from baseline to post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of the manic severity score obtained from the Young Mania Rating Scale (YMRS) questionnaire before, during and after light therapy treatment. Score range (min - max): 0-60. Higher score relates to worse maniac symptoms severity.
Change in suicidality symptoms from baseline to post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of the suicidality severity score obtained from the Columbia-Suicide Severity Rating Scale (C-SSRS) questionnaire before, during and after light therapy treatment. Suicidal ideation score range (min-max): 0-5. Higher score indicates greater severity of suicidal ideation (0 = no risk ; 5 = high risk).
Change in sleep quality from baseline to post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of sleep quality score obtained from the Pittsburgh Sleep Quality Index (PSQI) questionnaire before, during and after light therapy treatment. Score range (min-max): 0-21. Higher score indicates poorer sleep quality (0 = no sleep difficulties; 21 = major sleep difficulties).
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