Feasibility and Tolerability of Adjunct Chronotherapy in Depressed Inpatients

Acute depression, and suicidality continue to be significant causes of morbidity and
mortality, and frequently result in acute inpatient hospitalization. Currently available
treatments for depression have limitations for acute care including, either a slow onset of
action such as is the case of pharmacotherapy, or high cost and limited availability such as
is the case for ECT. This is exacerbated by ever shortening hospitalization times.
Subsequently many of the individuals who are admitted for depression are discharged weeks
before it can be expected for them to have symptomatic relief. Further more, in many cases
treatment results in the trial of multiple medications before an effective treatment regimen
is found (if such a treatment is found at all) (Rush, Trivedi et al. 2006). There is
subsequently a great need for effective anti-depressant therapies with rapid onset of
action, widespread availability, and cost effectiveness.

There is a consistent and expanding body of literature showing that chronotherapy is an
effective, and rapid treatment of acute depression(Wu, Kelsoe et al. 2009, Martiny,
Refsgaard et al. 2012, Echizenya, Suda et al. 2013). Published studies report response and
remission rates in the range of 41-61%, 24-59% respectively acutely. Chronotherapy is a
brief protocol that involves the combination of wake therapy (total sleep deprivation),
sleep phase advance (a shift to an earlier sleep schedule with gradual normalization), and
bright light therapy. The currently published reports have demonstrated efficacy in both
unipolar and bipolar depression, and there has been reported stability of results for as
long as 9 weeks (which was the longest designed study). Studies have been completed in real
world clinical populations, which have included co-morbid populations, with the only groups
showing a worsening of effect being those with psychotic depression (Benedetti, Zanardi et
al. 1999), and those with panic disorder(Roy-Byrne, Uhde et al. 1986). The treatment itself
has been well tolerated with a high percentage of individuals completing the procedure.

The current body of literature is encouraging, and the technique is being utilized
clinically in some facilities (including our own institution), however there are still
relatively few clinical trials published, and still unanswered questions that limit
widespread clinical utility. One such issue is related to the high percentage of published
trials performed outside of the US (although some have been done in the US). Because a high
percentage of the studies have been done in other countries it is not clear if this
procedure will translate well into the treatment paradigm in the US. Currently in the US,
inpatient admission is restricted to individuals with severe, often highly treatment
resistant disease that includes acute suicidality. To this writers knowledge there have not
been any studies that specifically address suicidality. It is also not clear if patients in
the US will tolerate the procedure. Tolerability has been addressed in many of the published
papers, and in general the procedure is tolerated well with few if any side effects,
however, again it is unclear how the procedure would be tolerated in clinical patients in
the US.

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 abuse/dependence that
requires detox.

- Current psychosis.

- Panic disorder.

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

- Medical illness that would make wake therapy intolerable, or significant cardiac
disease.

- Cataracts, glaucoma, or other intrinsic eye condition.

- Currently taking light sensitizing medications.

- Current pregnancy which is routinely tested for prior to admission.

- Mental retardation, or dementia.

- Untreated sleep disorder such as Obstructive sleep apnea, narcolepsy, or PLMD.