Practice Parameters for the Clinical Evaluation and Treatment of Circadian Rhythm Sleep Disorders. (2007). [PDF]
Timothy I. Morgenthaler, Teofilo Lee-Chiong, Cathy Alessi, Leah Friedman, R. Nisha Aurora, Brian Boehlecke, Terry Brown, Andrew L. Chesson, Vishesh Kapur, Rama Maganti, Judith Owens, Jeffrey Pancer, Todd J. Swick, Rochelle Zak, Standards of Practice Committee of the AASM, Practice Parameters for the Clinical Evaluation and Treatment of Circadian Rhythm Sleep Disorders, Sleep, Volume 30, Issue 11, November 2007, Pages 1445–1459.
3.1 General Recommendations for Evaluation of Circadian Rhythm Sleep Disorders
3.1.1 Use of a sleep log or diary is indicated in the assessment of patients with a suspected CRSD. (Guideline)
3.1.2 Actigraphy is indicated to assist in evaluation of patients suspected of CRSDs, including irregular sleep-wake disorder (ISWR), free-running disorder (FRD) (with or without blindness) (Option), and in advanced sleep phase disorder (ASPD), delayed sleep phase disorder (DSPD), and shift work disorder (SWD). (Guideline)
3.1.3 Actigraphy is useful as an outcome measure in evaluating the response to treatment for CRSDs. (Guideline)
3.1.4 There is insufficient evidence to recommend the routine use of the Morningness-Eveningness Questionnaire (MEQ) for the clinical evaluation of CRSDs. (Option)
3.1.5 Circadian phase markers are useful to determine circadian phase and confirm the diagnosis of FRD in sighted and unsighted patients but there is insufficient evidence to recommend their routine use in the diagnosis of SWD, JLD, ASPD, DSPD, or ISWR. (Option)
3.1.6 Polysomnography is indicated to rule out another primary sleep disorder in patients with symptoms suggestive of both a CRSD and another primary sleep disorder, but is not routinely indicated for the diagnosis of CRSDs. (Standard)
3.2 Recommendations for Evaluation and Treatments of Circadian Rhythm Sleep Disorders
3.2.3 Advanced Sleep Phase Disorder
3.2.3.1 There is insufficient evidence to recommend the use of the Morningness-Eveningness Questionnaire (MEQ) for the routine diagnosis of ASPD. [11.3.2] (Option)
3.2.3.2 Polysomnography is not routinely indicated for the diagnosis of ASPD. [11.3.3] (Standard)
3.2.3.3 There is insufficient evidence to recommend the use of circadian markers for the routine diagnosis of ASPD. [11.3.4] (Option)
3.2.3.4 Prescribed sleep/wake scheduling, timed light exposure, or timed melatonin administration are indicated as treatments for patients with ASPD. [11.4] (Option)
This recommendation is based on available evidence and committee consensus. One level 4 study78 achieved sleep advance with sleep scheduling.
There have been six studies using scheduled bright light as a treatment. One level 3 study73 found evening light exposure no more effective than placebo in shifting circadian phase. A level 2 study79 succeeded in reducing time in bed after awakening in the morning. Another level 2 study74 that used ICSD criteria to determine ASPD presence succeeded in improving sleep variables but another level 2 replication of this study75 did not. One level 477 and one level 2 study76 achieved post-treatment DLMO phase delays and improved sleep quality in patients with complaints of terminal insomnia.
Although there is a rationale for using melatonin for ASPD, there is no reported evidence in support of this treatment. Overall, the evidence for efficacy of these interventions is weak or conflicting, but the risks and costs entailed are low. As there are few alternatives, an individualized approach using one or more of these treatments with follow up to ascertain efficacy or side effects may be appropriate.
3.2.4 Delayed Sleep Phase Disorder
3.2.4.1 Polysomnography is not indicated in the routine assessment of DSPD. [12.3.5] (Standard)
3.2.4.2 Morning light exposure is indicated in the treatment of DSPD. Optimal timing, duration, and dosing of morning light treatment for DSPD remain to be determined. [12.4.2] (Guideline)
One level 180 and one level 281 study demonstrated that properly timed morning light exposure causes a phase advance of sleep onset time and circadian rhythms (CBTmin), and increases objectively determined daytime alertness. In the reviewed studies, 2500 lux for 2-3 hours prior to or at rise time was used. The effects of lower doses, blue light wavelengths, or other timings are not yet known. The treatments were generally well tolerated and of some beneficial effect, but more potent and less difficult to follow treatments are needed.
3.2.4.3. Chronotherapy (i.e., prescribed progressive delay in the schedule of sleep time until the desired sleep schedule is reached) may be useful for DSPD. [12.4.1] (Option)
This recommendation for chronotherapy is based only on two level 4 case report studies82,83 and committee consensus; there are no controlled trials supporting its efficacy or safety. Longer lasting and more practical alternatives are needed given that compliance with the treatment is difficult and lasting benefit has not been demonstrated.
3.2.4.4 Properly timed melatonin administration is indicated as a therapy for DSPD. [12.4.3] (Guideline)
This recommendation is supported by one level 184 two level 285,86 and one level 487 studies. Afternoon or evening administration of melatonin shifts circadian rhythms (indicated by dim light melatonin onset [DLMO] and core body temperature minimum, [CBTmin]) to an earlier time. Compared to placebo, melatonin treatment reduced sleep onset latency, but there was no change in total sleep time or subjective daytime alertness. As with other studies involving melatonin, the optimal timing and dosing of melatonin administration are not established. In the reviewed studies, three used 5 mg84,85,87 while one 86 used two strengths (0.3 mg and 3 mg). Effective times of administration varied between 1.5 and 6 hours prior to the habitual bedtime.
3.2.4.5. Vitamin B12 is not indicated in the treatment for DSPD. [12.4.4] (Guideline)
3.2.4.6 There is insufficient evidence supporting the use of hypnotic medications to promote sleep or the use of stimulant medications to promote alertness for DSPD. [12.4.5; 12.4.6] (Option)
Circadian Rhythm Sleep Disorders: Part II, Advanced Sleep Phase Disorder, Delayed Sleep Phase Disorder, Free-Running Disorder, and Irregular Sleep-Wake Rhythm (2007)
Sack RL, Auckley D, Auger RR, Carskadon MA, Wright KP Jr, Vitiello MV, Zhdanova IV. (2007). Circadian rhythm sleep disorders: part II, advanced sleep phase disorder, delayed sleep phase disorder, free-running disorder, and irregular sleep-wake rhythm. An American Academy of Sleep Medicine review. Sleep. 30(11):1484-501.
ASPD
11.4.2 Timed Light Exposure
In the largest study to date, involving 47 older adults diagnosed with ASPD (although the specific criteria used to make this determination are not clear), “enhanced evening light” (averaging 265 lux) administered for 2 to 3 hours was no more effective than placebo in counteracting advanced sleep phase (as indicated by actigraphy). Nevertheless, patients reported a subjective benefit (level 3).21 The light treatment in this study (265 lux) was not as intense as bright light treatment (2000 to 10,000 lux) used in many other studies, and the timing was earlier than usual (15:00 to 17:00). Moreover, the degree of baseline circadian advancement, as assessed by aMT6 acrophases, was unclear, as the authors used unspecified reference standards culled from their other investigations.
Bright evening light exposure produced similarly lackluster results in a treatment trial in patients with complaints of early-morning awakenings, although no physiologic phase markers were utilized. The treatment was administered for 30 minutes, beginning approximately 1 hour before subjects’ habitual bedtimes, for a duration of 3 weeks (level 2).27 As compared to the sham treatment condition, those receiving active treatment described subjective improvement in early morning awakenings, as manifested by an approximately 20 minute decrease of time in bed subsequent to final morning arising. No other differences were observed with respect to the additional subjective variables, or with respect to any of the actigraphic variables.
Greater success was demonstrated in a study of subjects with ICSD-1-defined ASPD, utilizing evening light therapy (4000 lux, 2-hour duration, between 20:00 and 23:00) for 12 consecutive days (level 2).22 A greater-than-two-hour CBTmin post-treatment delay was demonstrated, in association with an average delay in bedtime of 29 minutes, an approximately 13% increase in sleep efficiency, and a related decrease in wakefulness after sleep onset (WASO). Post-treatment sleep architecture changes were also noted in the form of increased REM latency, decreased percentage Stage 1 NREM sleep, and increased percentage Stage 2 NREM sleep. The control group demonstrated no significant changes in either sleep or circadian parameters.
However, in their most recent study, the same group, utilizing an essentially identical protocol failed to replicate many of these findings. Although treatment resulted in significant delays in both group CBTmin (94 minutes) and sleep onset (44 minutes), in addition to a significant increase in the phase angle of CBTmin and sleep midpoint by more than 1 hour, no other significant improvements in PSG-determined sleep parameters were obtained (level 2).23 Subsequently, patients received light therapy twice weekly for a 3-month period (maintenance treatment phase); they then demonstrated a trend toward reversion to the pre-treatment CBTmin (i.e., phase advance), and a lack of significant difference between any assessed parameter as compared with controls. Subjective sleep quality improved in the active group during maintenance treatment, but not in the control group. The authors proposed that the discrepancy in results may have been due to heterogeneous patient populations in their second study (a formal diagnosis of ASPD was not required, as it was in the first study), and/or unmonitored adherence to treatment.
Finally, capitalizing on the success of an earlier uncontrolled pilot investigation (level 4),25 a different group recently designed a study specifically involving individuals with isolated early-morning awakenings and assessed the effects of two consecutive nights of light therapy (2500 lux, administered for four hours from 20:00 to 01:00 (level 2).24 Both active and sham treatment groups had much earlier baseline CBTmin values than the aforementioned studies for which physiologic markers were available (active treatment CBTmin approximately 02:00). The active group exhibited a significant post-treatment delay of CBTmin of over two hours. Baseline DLMO values (as assessed by urinary aMT6) were referenced only in a figure (without raw data available), but also exhibited average post-treatment phase delays of approximately two hours in the active group. Sleep parameters (as assessed by actigraphy and sleep logs) demonstrated a significant decrease in actigraphically-determined WASO in the active treatment group at both 1- and 4-week follow-up periods, in addition to subjective (but not objective) improvement in total sleep time at the end of the 4-week follow-up period (90 minutes as compared with baseline, and 45 minutes as compared with sham treatment). There were otherwise few meaningful significant group differences with respect to sleep onset or offset times.
Conclusions: The available data on the treatment of ASPD (and the treatment of insomnia utilizing phototherapy) consists exclusively of evening light therapy. While objective results are overall conflicting, subjective improvements have been consistently demonstrated. Comparison of treatment effects is limited by the heterogeneous nature of the patient population, perhaps in part influenced by the ambiguous criteria for ASPD in the ICSD, variable use of established circadian phase markers, differing intensity and durations of treatments, and nonsystematic assessments of treatment compliance. Future studies would benefit from addressing these factors, in the context of protocols that are cognizant of practical clinical scenarios (e.g,. an established duration of nightly or maintenance treatments). The use of blue light, addressed in Part I, may also significantly influence treatment factors, possibly allowing for increased potency of the stimulus and/or a reduction in required exposure time, potentially increasing practical clinical application (and patient acceptance) of this treatment modality.28
11.4.3 Timed Melatonin Administration
There are no systematic reports of melatonin administration for ASPD, but consideration of the melatonin PRC provides a rationale for low-dose administration after early morning awakenings and upon final arising in the morning.29
Conclusion: There are insufficient data to assess the safety and efficacy of timed melatonin administration in the treatment of ASPD.
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12.0 DELAYED SLEEP PHASE DISORDER (DSPD)
12.4.2 Timed Light Exposure
Light exposure in the morning, on the advance portion of the light PRC, would be expected to shift circadian rhythms earlier, thereby correcting a pathological phase delay. Rosenthal et al. (level 2)46 treated 20 patients diagnosed with DSPD for two weeks using two hours of bright light exposure (2,500 lux) and two hours of ordinary light (300 lux) exposure in the morning (between 06:00 and 09:00) in a crossover design. The bright light treatment produced a significant phase advance of the core body temperature rhythm, although there was no attempt to minimize masking, as well as an increase in morning alertness as measured with the MSLT.
In a novel study, Cole, et al. (level 1)47 treated DSPD with an illuminated mask that provided light through closed eyelids during sleep. The light mask was reported as well tolerated, producing little sleep disturbance. The mask turned on (<0.01 lux) four hours before arising, ramped up for one hour, and remained on at full brightness until arising (2500 lux for active treatment, 0.1 lux for controls). The bright light treatment advanced the timing of aMT6s by one hour after 26 days of treatment, and advanced sleep onset times in the subset of patients with the most delayed phases.
Conclusion: Although the evidence is limited, light exposure treatment, timed to advance rhythms based on the light PRC, appears to be a rational and effective intervention for DSPD. In the clinical context, compliance may be a significant problem.
12.4.3 Timed Melatonin Administration
Melatonin administration in the afternoon or evening, during the phase advance portion of the melatonin PRC, would be expected to shift rhythms earlier, thereby correcting a pathological phase delay. This hypothesis was supported in an early study of limited sample size (N = 8), (level 2).48 In a large (N = 61), open-label study, those receiving 5 mg of melatonin given at 22:00 for six weeks reported significant benefit, but also a high rate of relapse when treatment was discontinued (level 4).49
In a double-blind, cross-over study, DSPD patients (N = 20) were treated with 5 mg melatonin or placebo, taken between 19:00 and 21:00 (time chosen by each patient) for four weeks (level 1).50 Two consecutive PSGs were performed during an imposed sleep schedule (24:00 to 08:00) on three occasions: at baseline (before treatment), then after each arm of treatment. Melatonin treatment led to normalization in the rhythm of aMT6s excretion compared to placebo, and significantly reduced sleep onset latency as determined by PSG. However, PSG-determined TST was not increased, nor were self-reported measures of daytime alertness improved.
A recent double-blind study tested two doses of melatonin (0.3 and 3 mg) vs. placebo (level 2).41 Circadian phase using DLMO and core body temperature minimum (CBTmin.) was measured before and after treatment. Treatment was administered between 1.5 and 6.5 hours prior to the DLMO for four weeks. Both doses advanced DLMO and CBTmin; the earlier the melatonin was administered relative to DLMO, the larger the phase advance, consistent with the reported melatonin PRC.51
Conclusion: The evidence is quite strong that melatonin, timed to promote a corrective phase advance, is an effective treatment for DSPD. Determining the optimal parameters for scheduling and dosing will require more study.
12.4.4. Vitamin B12
Some early case reports and smaller studies suggested that vitamin B12 might be useful for CRSDs by some unknown mechanism. This hypothesis was quite rigorously tested in a large (N = 55), multicenter, placebo-controlled trial in which Vitamin B12 (1 mg), or placebo, was administered to DSPD patients three times a day for four weeks (level 1).52 No benefit was seen from the sleep log data.
Conclusion: Vitamin B12 is not an effective treatment for DSPD.
12.4.5 Promoting Sleep with Hypnotic Medication
There is one report involving uncontrolled clinical observations indicating some benefit of hypnotic medications for DSPD (level 4).44
Conclusion: There is insufficient evidence to assess the safety and efficacy of hypnotic medication in the treatment of DSPD.
12.4.6 Promoting Alertness with Stimulant Medication.
A stimulant medication administered to promote alertness upon arising could be clinically justified, but there are no data on this practice.
Conclusion: There is no evidence to assess the safety and efficacy of stimulant medication in the treatment of DSPD.
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Auger, R.R., Burgess, H.J., Emens, J.S., Deriy, L.V., Thomas, S.M., Sharkey, K.M. (2015). Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders: Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD). An Update for 2015: An American Academy of Sleep Medicine Clinical Practice Guideline. Journal of Clinical Sleep Medicine, 11, 10, 1199-236. Free PMC Article. [PDF]
ASWPD
5.1.4a The TF suggests that clinicians treat adult ASWPD patients with evening light therapy (versus no treatment).
[WEAK FOR]
DSWPD
5.2.6.1a The TF suggests that clinicians treat DSWPD in adults with and without depression with strategically timed
melatonin (versus no treatment). [WEAK FOR]
5.2.6.2.1a The TF suggests that clinicians treat children and adolescents with DSWPD (and no comorbidities) with
strategically timed melatonin (versus no treatment). [WEAK FOR]
5.2.6.2.2a The TF suggests that clinicians treat children and adolescents with DSWPD comorbid with psychiatric
conditions with strategically timed melatonin (versus no treatment). [WEAK FOR]
5.2.9.2a The TF suggests that clinicians treat children and adolescents with DSWPD with post-awakening light
therapy in conjunction with behavioral treatments (versus no treatment). [WEAK FOR]
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5.1.4a The TF suggests that clinicians treat adult ASWPD patients with evening light therapy (versus no treatment).
[WEAK FOR]
Summary: No treatment trials of light therapy in ASWPD have been published since the 2007 Practice Parameters, which recommended this therapy as an OPTION. The largest effects were seen after a 12-day treatment of 2 hours of bright white broad spectrum light (~4,000 lux) from 2 light boxes (proximity to source not specified), timed to occur daily between 20:00 and 23:00, and ending before habitual bedtime.73
DSWPD
5.2.6.1a The TF suggests that clinicians treat DSWPD in adults with and without depression with strategically timed
melatonin (versus no treatment). [WEAK FOR]
Positive results were obtained with a 5 mg dose timed between 19:00–21:00 (no circadian-based timing), for a period of 28 days.90,93
5.2.6.2.1a The TF suggests that clinicians treat children and adolescents with DSWPD (and no comorbidities) with strategically timed melatonin (versus no treatment). [WEAK FOR]
Optimal results were obtained with a dose of 0.15 mg/kg, taken 1.5–2.0 hours prior to habitual bedtime, for 6 nights.
5.2.6.2.2a The TF suggests that clinicians treat children and adolescents with DSWPD comorbid with psychiatric
conditions with strategically timed melatonin (versus no treatment). [WEAK FOR]
A fast-release formulation of melatonin was utilized, with dosages ranging from 3–5 mg, taken between 18:00–19:00 (no circadian-based timing), for 4 weeks. In the pooled analysis, actigraphically assessed sleep onset time advanced in conjunction with an advance in the circadian phase marker (DLMO).
5.2.9.2a The TF suggests that clinicians treat children and adolescents with DSWPD with post-awakening light
therapy in conjunction with behavioral treatments (versus no treatment). [WEAK FOR]
Light therapy occurred via exposure to natural sunlight (when available), or with use of a white broad spectrum lamp (~1000 lux, proximity to source not specified), for ≥ 0.5 hours (2 hours maximum), with the time of administration
advanced by 0.5 hours daily from “natural” wake time, until a target time of 06:00 was reached. Light therapy was sub sequently discontinued, and behavioral interventions ensued.
5.2.9.1. Light/combination treatments for adults with DSWPD
There is no evidence to support efficacy of light therapy (provided by means other than a “light box”) in association
with concomitant behavioral instructions among adults.
American Academy of Sleep Medicine Clinical Guidelines
Auger, R.R., Burgess, H.J., Emens, J.S., Deriy, L.V., Thomas, S.M., Sharkey, K.M. (2015). Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders: Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD). An Update for 2015: An American Academy of Sleep Medicine Clinical Practice Guideline. Journal of Clinical Sleep Medicine, 11, 10, 1199-236. Free PMC Article. [PDF]
Practice Parameters for the Clinical Evaluation and Treatment of Circadian Rhythm Sleep Disorders. (2007). [PDF]
Dodson, E. R, & Zee, P. C. (2010). Therapeutics for Circadian Rhythm Sleep Disorders. Sleep Medicine Clinics. 5 (4): 701–715.
A Clinician’s Guide to Using Light Therapy, by Raymond W. Lam and Edwin M. Tam. New York: Cambridge University Press, 2009 [Amazon]
Up to Date - Delayed Sleep-Wake Phase Disorder
https://www.circadiansleepdisorders.org
van Geijlswijk, I. M., Korzilius, H. P., & Smits, M. G. (2010). The use of exogenous melatonin in delayed sleep phase disorder: a meta-analysis. Sleep, 33(12), 1605–1614.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2982730
https://www.ncbi.nlm.nih.gov/pubmed/29912983
https://www.ncbi.nlm.nih.gov/pubmed/30148726
https://www.ncbi.nlm.nih.gov/pubmed/16295212
https://www.ncbi.nlm.nih.gov/pubmed/27611743
https://www.ncbi.nlm.nih.gov/pubmed/24388969
https://www.circadiansleepdisorders.org/docs/DSPS-QandA.php
https://www.nhlbi.nih.gov/health-topics/circadian-rhythm-disorders
Faulkner, S. M., Bee, P. E., & Meyer N., et al. (2019) Light therapies to improve sleep in intrinsic circadian rhythm sleep disorders and neuro-psychiatric illness: A systematic review and meta-analysis. Sleep Med Rev, 46:108. [PubMed] [Full Text]
https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00085/full