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

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

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.

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.

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.