Rapid and sustained antidepressant response with sleep deprivation and chronotherapy in bipolar disorder.


This study combined one night of sleep deprivation with 3 days of bright light therapy and sleep phase advance as augmentation therapy for major depression in patients with bipolar disorder. The addition of these treatments, when compared with medication alone, was associated with significantly lower depression symptoms. This difference was first observed on Day 2, and was sustained throughout the study (Week 7).


  • N=49 outpatients with bipolar disorder and having a major depressive episode, defined as ≥18 on Hamilton Rating Scale for Depression (HRSD-24).
  • Patients randomized (3:2) to:
    • Chronotherapeutic augmentation treatment (CAT, n=32)
    • Medication only (MED, n=17)
  • CAT group participated in four inpatient nights, consisting of one sleep deprivation night plus three days of bright light therapy and sleep phase advance:
    • Sleep Deprivation (SD): participants kept awake for 33 hours (9am until 6pm the next day).
    • Bright Light Therapy (BL): 5,000 lux for 2 hours on the 3 mornings following sleep deprivation night.
    • Sleep Phase Advance (SPA): participants had 7 hours of sleep for the 3 nights following sleep deprivation, with start times pushed back by 2 hours each night (i.e. 6pm the first night, 8pm the second, 10pm the third). Thus, they had 7 hours of sleep during a 26-hour day.
  • All patients in both groups received antidepressants and mood stabilizers.
  • Setting: University of California Irvine and San Diego.
  • Patients and raters were not blinded to the sleep deprivation procedure.
  • Primary outcome: Abbreviated rating scale (HRSD-19) twice per day for the first week and weekly after that. Response defined as 50% decrease in HRSD score over baseline. Remission defined as response criteria plus HRSD rating ≤7 at end of 7 weeks.


  • CAT group showed significantly lower HRSD scores compared with MED group, based on repeated-measures mixed effects model analysis.
  • Significant benefit in the CAT group over the MED group was first observed on the second day of treatment, and was sustained through the end of the study (week 7).
  • HRSD-19 scores on Day 7 (P=0.001):
    • CAT: 10.2 (SD=7.3)
    • MED: 14.4 (SD=8)
  • HRSD-19 scores on Week 7 (P=0.02):
    • CAT: 10.1 (SD=9.6)
    • MED: 15.2 (SD=10.2)
  • While adverse events were rare, 2 CAT patients experienced a brief hypomanic switch that resolved in 24 hours without medication. There were no adverse events in the MED group.


Wu JC, Kelsoe JR, Schachat C, et al. Rapid and sustained antidepressant response with sleep deprivation and chronotherapy in bipolar disorder. Biol Psychiatry. 2009;66(3):298-301. doi:10.1016/j.biopsych.2009.02.018.

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