Correcting delayed circadian phase with bright light therapy predicts improvement in ADHD symptoms: A pilot study
Introduction
Attention-deficit/hyperactivity disorder (ADHD) is characterized by problems with attention, impulsivity and over-activity. The syndrome affects 4.5% of adults (Kessler et al., 2006), resulting in an estimated $3.6 billion loss in work costs (Birnbaum et al., 2005). More than 70% of children and adults with ADHD also report insomnia (Fargason et al., 2013; Fargason et al., 2011, Gruber et al., 2012, Kessler et al., 2006, Van der Heijden et al., 2005, Van Veen et al., 2010). The sleep disturbance is often due to circadian rhythm disruption characterized by delayed sleep in both children and adults, and psychiatric disorders, including ADHD, have been found to be associated with phase delay (Gamble et al., 2013, Lewy et al., 2006). Patients with ADHD demonstrate delays in: sleep-wake rhythms, nocturnal rise in melatonin, and early morning rise in cortisol (Baird et al., 2012, Novakova et al., 2011, Van der Heijden et al., 2005, Van Veen et al., 2010). Despite the significant comorbidity of ADHD and sleep disturbances, common treatment regimens such as stimulants do not address these sleep problems, and hence fail to achieve full symptom control of core ADHD symptoms. In fact, treatment with long-acting stimulant medications can shorten sleep duration, delay sleep-onset, and reduce circadian amplitude, all of which may negatively impact executive function and attention (Morash-Conway et al., 2016, Ironside et al., 2010). Additionally, circadian dysfunction and resultant disturbed sleep are associated with learning problems (Kopasz et al., 2010, Van der Heijden et al., 2005), poor driving performance (Anderson and Horne, 2013, Ftouni et al., 2013), depression (Lall et al., 2012, McCall et al., 2010, Taylor et al., 2005), and occupational dysfunction (Adan et al., 2012, Dagan, 2002), all of which are ADHD co-morbidities. As a result, there is an urgent need to develop non-pharmacological approaches to treat sleep disturbances, which often worsen attention deficits and impulsive behavior in adults with ADHD diagnosis.
When presented at the appropriate time-of-day, bright light therapy (BLT) has shown success for the treatment of a variety of sleep conditions (Crowley et al., 2004, Revell and Eastman, 2005, Smith et al., 2009, Wilhelmsen-Langeland et al., 2013, Wilhelmsen-Langeland et al., 2014, Wirz-Justice et al., 2013). A key characteristic of the endogenous circadian clock is the ability to synchronize 24-h rhythms to the light-dark cycle, such that early evening light exposure shifts wake-time to a later time (phase delay) while early morning light exposure shifts wake-time to an earlier time (phase advance) (Klein and Weller, 1970, Tamarkin et al., 1979). Well-timed light exposure can be used to shift sleep-wake rhythms earlier or later before/after transmeridian travel or before/after a change in shift schedule (Honma et al., 1991, Revell and Eastman, 2005). Therapeutic use of BLT in the morning to extend the light exposure period during the winter (mimicking summer-like conditions) alleviates depression in seasonal affective disorder (Burgess et al., 2004, Lieverse et al., 2011, Terman, 2006). Insomnia associated with delayed sleep phase syndrome is improved after administration of morning BLT (30 min) in a randomized controlled trial (Wilhelmsen-Langeland et al., 2013). Finally, combining BLT with total sleep deprivation and sleep phase advance (‘Triple Chronotherapy’) significantly reduced depression and suicidal ideation in an open-label, adjunctive therapy trial (Sahlem et al., 2014).
Our prior clinical trial demonstrated that delayed sleep timing (circadian phase delay) predicts ADHD symptom severity and that standard psychopharmacologic treatments for ADHD often do not completely control symptoms in participants with circadian rhythm delay (Gamble et al., 2013). These findings have not been translated into practical treatment applications such as BLT in patients with ADHD diagnosis. Thus, the aim of our study was to use BLT to manipulate the well-validated endogenous clock phase marker dim-light melatonin onset (DLMO) to explore the relationship between delayed circadian phase and ADHD symptoms. Understanding this relationship may highlight complementary or alternative mechanisms for clinical treatment.
Section snippets
Participants
In this study, all participants were between ages 19 and 64 and met the DSM-IV-TR criteria for ADHD (more restrictive than DSM-5 criteria) with a mean age of 36.1 ± 13.2. Patients taking psychoactive medication for any condition other than ADHD or who were diagnosed with a co-morbid psychiatric disorder, sleep apnea, light-sensitive skin condition, ocular disorder or were shift-workers were excluded. Participants were recruited from the UAB Outpatient Psychiatry clinic during November
Results
A total of 19 participants completed the protocol. DLMO data from 3 participants were not analyzable due to low melatonin levels (N = 2) and light exposure during collection (N = 1). As predicted, BLT advanced the phase of DLMO by 31 min [mean time (SEM), 20:36 (0:21) advanced to 20:05 (0:20)] and mid-sleep time by 57 min [4:37 (0:22) advanced to 3:40 (0:16); paired t-tests, p = 0.002 and 0.004, respectively; Fig. 2). The net effect of these two outcomes produced a significantly more narrow
Discussion
Despite the association of delayed sleep timing with ADHD symptom severity and the inadequacy of standard psychopharmacologic treatments for ADHD in participants with circadian rhythm delay (Gamble et al., 2013), the effectiveness of BLT as a treatment for patients with ADHD diagnosis has not previously been assessed. As hypothesized, BLT advanced DLMO and mid-sleep in adults with ADHD, and these advances were associated with decreased ADHD symptoms, including hyperactive-impulsive symptoms.
Conclusion
This open-label pilot study suggests that BLT is a feasible treatment for adults with ADHD and may be a successful complementary treatment for delayed sleep timing and symptoms of ADHD in adults. A randomized, placebo-controlled trial is needed to assess futher treatment effects.
Financial/material support
UAB Health Services Foundation General Endowment Fund Actigraphy Program and UAB Psychiatry departmental funds (Birmingham, AL, USA).
Disclosures
All authors have no direct or indirect affiliations or financial interests in connection with the content of this paper to disclose.
Acknowledgments
We would like to thank Dr. James Meador-Woodruff, M.D. (UAB Department of Psychiatry) for general support for this project, and Dr. Richard Shelton, M.D. (UAB Department of Psychiatry) for critical review of the study and for editing this letter. Drs. Meador-Woodruff and Shelton have no financial disclosures for this project.
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