Elsevier

Journal of Psychiatric Research

Volume 59, December 2014, Pages 101-107
Journal of Psychiatric Research

Adjunctive triple chronotherapy (combined total sleep deprivation, sleep phase advance, and bright light therapy) rapidly improves mood and suicidality in suicidal depressed inpatients: An open label pilot study

https://doi.org/10.1016/j.jpsychires.2014.08.015Get rights and content

Highlights

  • Few rapid treatments exist for the treatment of depression.

  • Triple Chronotherapy shows promise as a rapidly acting adjunct antidepressant.

  • Despite its promise, Triple Chronotherapy lacks safety data in suicidal patients.

  • We found the use of Triple Chronotherapy is safe in depressed suicidal inpatients.

Abstract

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. To date no studies have explored the impact of the intervention on unipolar depressed individuals with acute concurrent suicidality. Participants were suicidal inpatients (N = 10, Mean age = 44 ± 16.4 SD, 6F) with unipolar depression. In addition to standard of care, they received open label Triple Chronotherapy. Participants underwent one night of total sleep deprivation (33–36 h), followed by a three-night sleep phase advance along with four 30-min sessions of bright light therapy (10,000 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 protocol completion on 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 ± 4.2 SD at baseline to a mean of 9.4 ± 7.3 SD on day five (p = .002) with six of the ten individuals meeting criteria for remission. CSSRS scores dropped from a mean of 19.5 ± 8.5 SD at baseline to a mean of 7.2 ± 5.5 SD 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.

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 depression. Suicide is the 10th leading cause of death in the United States, and is even higher among younger individuals between 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 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 (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, 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). 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. That study used a slightly different variation of chronotherapy that included three nights of sleep deprivation every other night with three light therapy sessions, combined with lithium (Benedetti et al., 2014). The lack of data utilizing Triple Chronotherapy in acutely suicidal patients significantly limits its utility in the United States, where few non-suicidal patients are admitted to the inpatient unit. Furthermore, published trials to this point have excluded those with comorbid illness, which also limits the clinical usefulness of this intervention to a minority of patients. We subsequently sought to determine if adjunctive Triple Chronotherapy was safe and feasible in acutely depressed and suicidal inpatients.

Section snippets

Participants

We included participants with non-psychotic unipolar, or bipolar depression (who were on a therapeutic dose of a mood stabilizer), age 18–75. We excluded patients who were in a mixed state, had active psychosis, had active panic disorder, were actively withdrawing from a substance of abuse, had a history of seizures, or had active unstable medical or neurologic illness.

We recruited participants from inpatient units at the Medical University of South Carolina (MUSC) Institute of Psychiatry (IOP)

Results

As compared to baseline there was a statistically and clinically significant decrease in both clinician, and self rated scales of depression and suicidal ideation. The 17-Item Hamilton depression scale went from an average of 24.7 ± 4.2 SD at day 0, to a final score of 9.4 ± 7.3 SD on day 4. Six out of ten participants met criteria for remission on the Ham17 (60%). Sixty-percent met criteria for response (Fig. 3, Fig. 4). The Columbia Suicide Severity Index went from an average of 19.5 ± 8.5 SD

Discussion

This small, open label pilot study suggests that adjunctive Triple Chronotherapy is safe and tolerable in acutely suicidal, unipolar depressed inpatients. These results complement and extend the recently published study demonstrating safety of another variant of Chronotherapy in suicidal Bipolar Depressed inpatients (Benedetti et al., 2014). This conclusion, along with any conclusion regarding treatment efficacy, must however be made in the context of significant experimental limitations, with

Role of the funding source

Support was provided by the Medical University of South Carolina Resident Research Training Program (DART program), which was funded by National Institute on Drug Abuse (NIDA) R25 DA020537-06 (PI's Back and Brady). Besides providing mentorship that assisted in experimental design and implementation, the funding source did not influence the project.

Author contributions

Gregory L. Sahlem was the Primary investigator of the study. He contributed in experimental design, regulatory procedures, data collection, data analysis, and manuscript preparation.

Benjamin Kalivas contributed in experimental design, data analysis, and manuscript preparation.

James B. Fox contributed in recruitment, and manuscript preparation.

Kayla Lamb contributed to regulatory procedures, and manuscript preparation.

Amanda Roper contributed in experimental design, and manuscript preparation.

Conflict of interest

There is no Conflict of Interest.

Acknowledgments

We would like to thank the acute inpatient team at the Institute of Psychiatry of the Medical University of South Carolina for their tireless effort. Without your help this study could not have occurred. We would also like to thank the Drug Abuse Research Track (DART) program at the Medical University of South Carolina with special thanks to Drs.Back and Brady, along with the grant that supports it (NIDA R25 DA020537-06 (PI's Back and Brady)).

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