Wake Therapy in the Treatment of Depression

Combined Wake Therapy, Light Therapy, and Lithium for Bipolar and Refractory Depression

This pilot study seeks to replicate previous findings that sleep deprivation results in marked improvement in depression symptoms, as well as to test whether concurrent treatment with Light Therapy and Lithium are successful in locking in and maintaining therapeutic effects in both bipolar and unipolar depressed subjects.

Both refractory depression and bipolar depression are difficult to treat. A night of complete sleep deprivation has been shown to result in marked improvement in 60% of depressed patients, although maintenance of therapeutic effects have not been sustained with wake therapy alone. This pilot study will assess the effectiveness of wake therapy in treating both bipolar depression (5 participants)and major depression (5 participants), as well as the effectiveness of concomitant light therapy and lithium in maintaining the therapeutic effects. Participants will undergo direct observation in the hospital for one week during initial treatment with alternating nights of sleep deprivation, light therapy and lithium treatment, and then will be seen weekly as outpatients for 6 weeks.

Inclusion Criteria:

1. current major depressive episode (MDD, BP-I or BP-II)
2. if not BP-I or BP-II, treatment refractory to ≥ 2 adequately used antidepressants having different mechanisms
3. If BP-I or BP-II, treatment refractory to ≥ 1 standard treatment, such as lithium or valproate
4. physically healthy
5. age 18-75
6. not taking current antidepressants(antidepressants deemed effective will not be discontinued

Exclusion Criteria:

1. medically unstable condition
2. past intolerance of lithium (bipolar only)
3. history of (or current) psychosis or epilepsy
4. current (past six months) drug or alcohol abuse/dependence
5. pregnancy
6. contraindication to lithium (bipolar only)
7. significant retinal pathology (e.g., retinitis pigmentosa, macular degeneration)
8. currently taking effective antidepressant
9. cognitive dysfunction
10. Parkinson's Disease
11. Thyroid Stimulating Hormone > 5 milli International Units/Liter
12. left ventricular hypertrophy
13. symptomatic mitral valve prolapse
14. abnormal creatinine