Chronotherapy Randomized Controlled Trial

There is a consistently reported, rapid antidepressant response to a single night of total
sleep deprivation in both unipolar, and bipolar depression. The clinical utility of this
technique has been limited however, because responders have typically relapsed rapidly
following recovery sleep. The addition of pharmacotherapy, sleep phase advance (a shift to an
earlier sleep schedule with normalization over three days), and bright light therapy to sleep
deprivation have each demonstrated efficacy in preventing relapse into depression. Combined
total sleep deprivation, sleep phase advance, and bright light therapy, dubbed Triple
Chronotherapy along with concomitant pharmacotherapy has demonstrated a rapid improvement in
depressive symptoms that has remained durable for as long as 9 weeks post intervention. If
the early, encouraging results of Triple Chronotherapy hold up to further study, the
technique represents a near ideal inpatient treatment, as it is inexpensive, relatively easy
to carry out, and has minimal side effects.

Despite encouraging early results, only one published report has attempted to use triple
chronotherapy in suicidal patients, and in that trial only bipolar depressed patients were
included, and one single variation of chronotherapy was tested (Three nights of sleep
deprivation every other night with three light therapy sessions, combined with lithium). The
lack of data in acutely suicidal patients significantly limits the utility of this
intervention in the United States, where few non-suicidal patients are admitted. Published
trials to this point have also excluded those with comorbid illness, which also limits the
clinical usefulness of this intervention to a minority of patients. Furthermore there are
sparse randomized adequately controlled trials, and still limited durability data on the
technique.

We recently explored the tolerability and feasibility of the technique on acutely depressed
and suicidal inpatients admitted to our inpatient unit with encouraging results. We
subsequently propose to further explore the utility of this technique by piloting its effect
compared to an active sham condition to determine if further study is indicated. Should
further study be warranted, we hope to use the collected pilot data to determine the
necessary number of participants to detect an effect.

Inclusion Criteria:

- A current episode of non-psychotic major depression

- Currently hospitalized

- Age greater than 18

- If bipolar illness, must not be a mixed state, and must be on a therapeutic dose of a
mood stabilizer

Exclusion Criteria:

- Urine drug screen positive for cocaine, or current alcohol/dependence that requires
detox

- current psychosis

- Panic Disorder

- Severe Borderline Personality Disorder

- A history of seizures, uncontrolled severe headaches, stroke, or other neurologic
illness that produces either gait abnormalities or lowered seizure threshold

- Medical illness that would make wake therapy intolerable

- Cataracts, glaucoma, or other intrinsic eye condition

- Currently taking light sensitizing medications

- Current pregnancy

- Mental retardation or dementia

- Untreated sleep disorder such as Obstructive Sleep Apnea(OSA), narcolepsy, or periodic
limb movement disorder(PLMD) that results in excessive sleepiness

- Currently receiving electroconvulsive therapy (ECT)