Bright Light Therapy in the Treatment of Non-seasonal Bipolar Depression

Study Overview
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Brief Summary
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Bipolar disorder (BD) is a severe brain disorder characterized by the recurrence of mood episodes. Depressive episodes in BD are frequently refractory and clinicians have few treatment options. Bright light therapy (BLT, also named phototherapy) is a promising emerging antidepressant strategy that is lacking evidence-based guidelines for its prescription in BD, including to avoid side effects such as manic switches. In this context, this study aimed to evaluate modalities of the BLT dosage (time of exposure) escalation depending on the tolerance (manic symptoms) in two groups exposed either during the morning or at mid-day.

Detailed Description
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Bipolar disorder (BD) is a severe brain disorder characterized by the recurrence of mood episodes. Patients presenting with BD spend more time with depressive symptoms than with manic ones, which have a major impact on the quality of life and is associated with poorer outcomes including recurrences and suicide. In addition depressive phases in BD are frequently refractory and clinicians have few treatment options. Bright light therapy (BLT, also named phototherapy) is the first line treatment for depression with seasonal patterns and show promising results in the treatment of non-seasonal depressions. More evidence in non-seasonal depressions is expected, especially in BD. Moreover, some specificities linked to BD, such as the manic switch, warrant evidence-based therapeutic guidelines and so deserve more studies in BD. Preliminary reports suggest that morning exposure may induce manic switches, and that mid-day exposures may be associated with a decreased risk of manic switch. Different dose-titration protocols have also not been compared, and data are lacking. In this context, this study aimed to evaluate modalities of the BLT dosage (time of exposure) escalation depending on the tolerance (manic symptoms) in two groups exposed either during the morning or at mid-day.

Official Title
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Bright Light Therapy in the Treatment of Non-seasonal Bipolar Depressive Episode of Bipolar Disorder: A Dose Research Phase I/II Trial

Conditions
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Bipolar Depression

Intervention / Treatment
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* Device: Light


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be aged from 18 to 55 year-old. Patients must read and understand French language, and must provide written informed consent. Patients must be inpatients or outpatients followed in psychiatry for a major depressive episodes. Patients must have a diagnosis of bipolar disorder, type I or II, according to the DSM-5 and determined by a SCID. Patients must have a major depressive episode, at least of moderate intensity, according to the DSM-5, with a MADRS total score ≥20 and determined by a SCID. Patients must have a mood stabilizer since at least 4 weeks at standard dosage (lithium, or sodium valproate, or second generation antipsychotics such as quetiapine, aripiprazole, olanzapine). Female patients must be using a medically accepted means of contraception. Patients must be affiliated to the social security scheme. Exclusion Criteria: Patients under guardianship or deprivation of liberty by administrative or judicial decision Seasonal pattern of major depressive episode according to DSM-5 criteria. Psychotic, mixed, or catatonic characteristics according to DSM-5 criteria High suicidal risk assessed by the Columbia Scale of Suicide Risk Severity (C-SSRS) Not stabilized comorbidities (addictive disorders according to the DSM-5 criteria or other decompensated general medical cause). Ophthalmic pathology (cataract, macular degeneration, glaucoma, retinitis pigmentosa) and diseases affecting the retina (retinopathy, diabetes, herpes, etc.). Photosensitive treatment, including the following treatments: Cyclins (Vibramycin®, Doxycycline®) Amiodarone (Cordarone®, Amiodarone®) Phenothiazines (Largactil®, Modecate®, Nozinan®, Melleril®, Trilafon®) Methotrexate (Methotrexate®) Sulfamides (antibiotics, diuretics or hypoglycemic agents) Chloroquine (Nivaquine®) Some anti-inflammatories (Apranax®, Indocid®) Psoralens used in puvatherapy Isotretinoin (Roaccutane® and generics) Verteporfin (Visudyne®). Lactating or pregnant women (pregnancy urine positive test). Subjects who have already used light therapy in the last 6 months. Therapeutic resistance of the current major depressive episode (≥2 traditional antidepressants such as SSRI, IRSNA, MAOI or tricyclic, at effective therapeutic dosage for more than 6 weeks) Use of another antidepressant strategy than the mood stabilizer, including antidepressants of all classes (which will have to be stopped before the initiation of light therapy) and psychotherapy with onset <1 month.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Dose finding study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Morning group<br>Exposition at 8 a.m +/- 30 min, during 10 active weeks, and assessed 6 months after this intervention | Device: Light<br>* Placebo light (50 Lux) during 1 week and then active bright light with glasses using a dosage escalation (inter- and intra-subject) of 7.5, 10, 15, 30 and 45 min<br>|
| Active Comparator: Mid-day group<br>Exposition at 8 a.m +/- 30 min, during 10 active weeks, and assessed 6 months after this intervention. | Device: Light<br>* Placebo light (50 Lux) during 1 week and then active bright light with glasses using a dosage escalation (inter- and intra-subject) of 7.5, 10, 15, 30 and 45 min<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mania Score | The Young Mania Rating Scale (YMRS) will be used as a measure of tolerance reflecting change in YMRS total scores at each week over the 10 weeks (Total score ≥ 12 defining an hypomanic switch). | 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Depression Score | The Montgomery-Asberg Depression Rating Scale (MADRS) will be used as a measure of efficacy reflecting changes from baseline to endpoint | 6, 8 and 10 weeks | 
| Change in Clinical Global Impressions (CGI) | The Clinical Global Impressions (CGI) will be used as a measure of efficacy reflecting changes from baseline to endpoint | 6, 8 and 10 weeks | 
| Change in tolerance | YMRS will be used to evaluate hypomanic switch at 3 days after each duration of exposition change | 1, 2, 3, 4, 5, 6, 8 and 10 weeks | 
| Acceptability | measured by auto-questionnaire made by the investigators | 1, 2, 3, 4, 5, 6, 8 and 10 weeks | 
| MADRS | The MADRS will be used to evaluate changes of depressive symptoms from baseline | 1, 2, 3, 4, 5, 6, 8 and 10 weeks, and then at 6 months | 
| Clinical Global Impressions (CGI). |  | 1, 2, 3, 4, 5, 6, 8 and 10 weeks, and then 6 months | 
| Columbia-Suicide Severity Rating Scale (C-SSRS) |  | 1, 2, 3, 4, 5, 6, 8 and 10 weeks, and then 6 months | 
| Quick Inventory of Depressive Symptomatology (QIDS SR-16) |  | 1, 2, 3, 4, 5, 6, 8 and 10 weeks, and then 6 months | 
| Altman Self-Rating Mania Scale (ASRM). |  | 1, 2, 3, 4, 5, 6, 8 and 10 weeks, and then 6 months | 
| Pittsburgh Sleep Quality Index (PSQI). |  | 1, 2, 3, 4, 5, 6, 8 and 10 weeks, and then 6 months | 
| Composite Scale of Morningness (CSM). |  | 1, 2, 3, 4, 5, 6, 8 and 10 weeks, and then 6 months | 
| Circadian Type Inventory (CTI). |  | 1, 2, 3, 4, 5, 6, 8 and 10 weeks, and then 6 months | 
| Epworth Sleepiness Scale (ESS). |  | 1, 2, 3, 4, 5, 6, 8 and 10 weeks, and then 6 months | 
| Side effects: PRISE-M |  | 1, 2, 3, 4, 5, 6, 8 and 10 weeks, and then 6 months |