Previous studies have demonstrated that combined total sleep deprivation (Wake therapy)

Previous studies have demonstrated that combined total sleep deprivation (Wake therapy) sleep phase advance and bright light therapy (Triple Chronotherapy) produce a rapid and sustained antidepressant effect in acutely depressed individuals. one night of total sleep deprivation (33-36 hours) followed by a three-night sleep phase advance along with four 30-minute sessions of bright light therapy (10 0 lux) each morning. Primary outcome measures included the 17 item Hamilton depression scale (HAM17) and the Columbia Suicide Severity Rating Scale (CSSRS) which were recorded at baseline prior to total sleep deprivation and at IOX 2 protocol completion on IOX 2 day five. Both HAM17 and CSSRS scores were greatly reduced at the conclusion of the protocol. HAM17 scores dropped from a mean of 24.7±4.2SD at baseline to a mean of 9.4±7.3SD on day five (p=.002) with six of the ten individuals meeting criteria for remission. CSSRS scores dropped from a mean of 19.5±8.5SD at baseline to a mean of 7.2±5.5SD on day five (p=.01). The results of this small pilot trial demonstrate that adjunctive Triple Chronotherapy is feasible and tolerable in acutely suicidal and depressed inpatients. Limitations include a small number of participants an open label design and the lack of a comparison group. Randomized controlled studies are needed. Keywords: Sleep deprivation Suicidal Ideation Chronotherapy Depression phototherapy Inpatients 1 Introduction Major depressive disorder is a neuropsychiatric condition that consists of core symptoms including a persistently depressed mood anhedonia sleep disruption anergia poor concentration guilt hopelessness appetite changes and suicidal ideation. Currently there are no commonly used rapid treatments for IOX 2 depression. Suicide is the 10th leading cause of death in the United States and is even higher among younger individuals between IOX 2 the ages of 10-24 where it is the second leading cause (Heron 2013 Untreated depression is known to be associated with suicide risk with estimates that 60% of all suicides are associated with inadequately treated depression (Mann et CBFA2T1 al. 2005 There is an apparent stratified risk of suicide in those who have been admitted to the inpatient unit for depression with those who have suicidal thoughts or suicide attempts posing the highest lifetime risk of committing suicide (Bostwick and Pankratz 2000 Depression is a major medical issue both domestically and abroad. Depression is the 4th leading cause of disability in the world and has an approximate lifetime prevalence of 16.5% in the United States(Kessler et al. 2003 Murray and Lopez 1996 Pharmacotherapy and psychotherapy are the most commonly used treatments but only approximately 67% of non treatment resistant depressed individuals achieve remission with medications or psychotherapy taking an average of 5-7 weeks to achieve remission in those who find an effective regimen(Rush et al. 2006 Even electroconvulsive therapy (ECT) which is our most dependable and effective treatment still takes 2-3 weeks for therapeutic benefit and has limited availability and cognitive side effects IOX 2 (Sackeim et al. 2007 Although there are promising newer treatments such as repetitive transcranial magnetic stimulation (rTMS) (George et al. 2014 and ketamine (Caddy et al. 2014 there are at this time no commonly used treatments that rapidly treat depression. Studies have consistently reported a rapid antidepressant response to total sleep deprivation in both unipolar and bipolar depression first studied by (Pflug and Tolle 1971 and reviewed extensively by (Wu and Bunney 1990 Wirz-Justice et al. 2005 and Benedetti et al 2007 The clinical utility of this technique is limited however because responders typically relapse rapidly following recovery sleep. The addition of pharmacotherapy (Benedetti et al. 2001 Colombo et al. 2000 Smeraldi et al. 1999 Martiny et al. 2012 Shelton and Loosen 1993 Szuba et al. 1994 Wu et al. 2009 sleep phase advance (Riemann et al. 1999 Echizenya et al. 2013 and bright light therapy(Echizenya et al. 2013 Martiny et al. 2012 Martiny et al. 2013 Neumeister et al. 1996 Wu et al. 2009 to sleep deprivation have each demonstrated efficacy in preventing some individuals from relapsing into depression. Some early studies have reported that combined total sleep deprivation sleep phase advance and bright light therapy dubbed Triple Chronotherapy along with concomitant pharmacotherapy produces a rapid improvement in depressive symptoms which endures for as long as 9 weeks (Echizenya et al. 2013 Martiny et al. 2012 Wu et al. 2009 IOX 2 If.