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Complete sleep-wake cycle reversal related to ADHD detected by actigraphy

August 2013
Annals of Clinical Psychiatry 25(3):E8-E9

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PubMed

Authors:

Rachel E Fargason

University of Alabama at Birmingham

Karen L Gamble

University of Alabama at Birmingham

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ANNALS OF CLINICAL PSYCHIATRY

LETTERS TO THE EDITOR

August 2013 | Vol. 25 No. 3 | Annals of Clinical PsychiatryE8

Complete sleep-wake

cycle reversal related

to ADHD detected by

actigraphy

Rachel E. Fargason, MD; Brittney A. White, MS;

Karen L. Gamble, PhD

KEYWORDS: CRSD, ADHD, actigraphy, insomnia

Insomnia often goes untreated despite adverse mood

and neurobehavioral effects.1 A key objective in

DSM-5 is improved management of sleep disorders

comorbid with psychiatric conditions.1 Circadian rhythm

sleep disorder (CRSD) occurs in 70% of patients with

attention-deficit/hyperactivity disorder (ADHD).2 We

present a case of severe CRSD, delayed sleep phase type

in a patient with ADHD, which was undetected before

actigraphy, to increase clinicians’ awareness of this

common, albeit neglected, condition. We also discuss

validated actigraphic sleep assessment devices that may

help detect this condition. Actigraphy’s advantages over

polysomnography have led to increased use of actigraphy

in research and sleep clinic settings.3 Actigraphic smart-

phone applications and commercial accelerometers

(Sleep Cycle®, UP Wristband®, Sleep Manager Pro®, The

One™FitBitz) are available to the general public.

High sensitivity for circadian measures and sleep-

onset/offset times make actigraphy particularly suitable

for sleep schedule disorders, such as CRSD.3 Even inex-

pensive products that detect subtle nighttime move-

ment data from the accelerometer in smartphones can

generate graphs of sleep-wake cycles. Validity measures

for each device must be assessed individually. Actiwatch

is a continuously worn, motion-sensing accelerometer.3

Activity counts are analyzed by software to produce

objective sleep quality data and graphs of sleep-wake

cycles over weeks.1 Sleep diaries enhance validity.

Case Report

Mr. J, age 31, presents with lifelong complaints of dis-

tractibility, restlessness, anergia, fatigue, and academic

and social underperformance. Sleep history reveals

chronically late bedtimes resulting in shortened sleep,

but no associated distress or impairment. Mr. J previ-

ously underwent inpatient substance treatment because

he used alcohol excessively every night to induce sleep;

he has been abstinent of alcohol for a decade. Mental

status reveals a fidgety, cheerful, euthymic, slightly

tangential man. He was diagnosed at this time with

ADHD persisting since early childhood (by DSM-IV-TR)

without other psychiatric comorbidity and entered an

ADHD-insomnia trial unmedicated.4 Mr. J’s participa-

tion in the trial was terminated early because research-

ers discovered complete sleep-wake cycle reversal by

actigraphy. See the FIGURE for displays of one week of Mr.

J's sleep-wake patterns.

Mr. J underreported his sleep problems. Patients

with insomnia often misperceive their actual sleep

states.5 CRSD was exacerbating Mr. J’s dysfunction

and needed to be stabilized before treating his ADHD.

Circadian disorders can negatively impact work and

social performance1; excessive tardiness put Mr. J’s job

at risk. ADHD severity correlates positively with circa-

dian delay.2 Most insomnia patients attempt indepen-

dent treatment using over-the-counter medications

or alcohol.1 In Mr. J’s case, untreated CRSD led to self-

medication and reliance on alcohol.

We advanced the delayed sleep phase using morn-

ing-time light therapy, dim evening lighting, and 8

mg/d of ramelteon—a melatonin agonist with hypnotic

and circadian-entraining effects4—taken at the desired

bedtime. These measures facilitated a sustained 11 

bedtime and 8  rise time. Mr. J’s case is not rare; 8.3%

of ADHD-insomnia patients have severe, undetected

sleep disorders that can only be discovered with actigra-

phy.4 Reliable actigraphy instruments inform diagnostic

and treatment decisions. ■

DISCLOSURES: The authors report no financial relation-

ship with any company whose products are mentioned

in this article or with manufacturers of competing

products.

ACKNOWLEDGEMENT: This study was supported by a

University of Alabama HSF General Endowment Fund

Grant.

ANNALS OF CLINICAL PSYCHIATRY 2013;25(3):E8-E9

AACP.com

ANNALS OF CLINICAL PSYCHIATRY

LETTERS TO THE EDITOR

Annals of Clinical Psychiatry | Vol. 25 No. 3 | August 2013 E9

Rachel E. Fargason, MD

Department of Psychiatry

and Behavioral Neurobiology

University of Alabama School of Medicine

Birmingham, AL, USA

Brittney A. White, MS

Department of Psychiatry

and Behavioral Neurobiology

University of Alabama School of Medicine

Birmingham, AL, USA

Karen L. Gamble, PhD

Department of Psychiatry

and Behavioral Neurobiology

University of Alabama School of Medicine

Birmingham, AL, USA

CORRESPONDENCE: Rachel Fargason, MD, 3rd Floor Callahan Eye Hospital, 1720 University Boulevard,

Birmingham, AL 35294 USA, E-MAIL: rfargason@uab.edu

1. Wirz-Justice A, Bromundt V, Cajochen C. Circadian

disruption and psychiatric disorders: the importance of

entrainment. Sleep Med Clin. 2009;4:273-284.

2. Gamble KL, May RS, Besing RC, et al. Delayed sleep

timing and symptoms in adults with attention-deficit/

hyperactivity disorder: a controlled actigraphy study.

Chronobiol Int. 2013;30:598-606.

3. Sadeh A. The role and validity of actigraphy in sleep

medicine: an update. Sleep Med Rev. 2011;15:259-267.

4. Fargason RE, Gamble K, Avis KT, et al. Ramelteon

for insomnia related to attention-deficit hyperactivity

disorder. Psychopharmacol Bull. 2011;44.

5. Bianchi MT, Klerman EB. Sleep misperception in

healthy adults: implications for insomnia diagnosis. J

Clin Sleep Med. 2012;8:547-554.

REFERENCES

FIGURE

Actigraphy studya of CRSD delayed due to ADHD (left) and in a normal control (right)

aActiwatch AW-64 Actigraphy System/Actiware-Sleep version 5.04 Sleep Scoring Software, Philips Respironics, Murrysville, PA; ClockLab Analysis software: Actimetrics, Wilmette, IL.

ADHD: attention-deficit/hyperactivity disorder; CRSD: circadian rhythm sleep disorder.

Black tick marks indicate activity. Note marked delay in sleep periods (represented by darkened areas) in relation to nighttime.

Average bedtime is 5:09 am, rise-time is 1:24 pm. The comparison actigraph demonstrates consolidated sleep during dark-time.

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Reports of sleep disturbances in attention deficit hyperactivity disorder (ADHD) are common in both children and adults; however, the aetiology of such disturbances is poorly understood. One potentially important mechanism which may be implicated in disrupted sleep in ADHD is the circadian CLOCK, a known key regulator of the sleep/wake cycle. In this systematic review, we analyse the evidence for circadian rhythm changes associated with ADHD, as well as assessing evidence for therapeutic approaches involving the circadian CLOCK in ADHD. We identify 62 relevant studies involving a total of 4462 ADHD patients. We find consistent evidence indicating that ADHD is associated with more eveningness/later chronotype and with phase delay of circadian phase markers such as dim light melatonin onset and delayed sleep onset. We find that there is evidence that melatonin treatment may be efficacious in addressing ADHD-related sleep problems, although there are few studies to date addressing other chronotherapeutic approaches in ADHD. There are only a small number of genetic association studies which report linkages between polymorphisms in circadian CLOCK genes and ADHD symptoms. In conclusion, we find that there is consistent evidence for circadian rhythm disruption in ADHD and that such disruption may present a therapeutic target that future ADHD research might concentrate explicitly on.

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Ramelteon for Insomnia Related to Attention-Deficit/Hyperactivity Disorder (ADHD)

Article

Full-text available

May 2011
Psychopharmacol Bull

Objectives: This study evaluated the efficacy of ramelteon for insomnia in adult subjects with ADHD. Experimental design: For this randomized, double-blind, placebo-controlled crossover trial, 8 mg of ramelteon was given nightly, within three hours of bedtime, to ADHD-insomnia subjects confirmed by DSM-IV-TR, ADHD-RS, MINI, and clinical interview. All subjects underwent two weeks each of ramelteon and placebo. Objective sleep measures were obtained by actigraphy. Subjective measures included: the Epworth Sleepiness Scale (ESS) and ADHD-RS. Principal observations: Of 36 subjects entering the study, 58% met criteria for circadian rhythm sleep disorder (CRSD), delayed sleep phase type. During ramelteon period, mid-sleep time, an indicator of circadian phase, occurred significantly earlier, by ~45 minutes compared to placebo period. An association was noted between the magnitude of the sleep phase advance and the timing of ramelteon administration in relationship to sleep start time, but did not reach statistical significance; maximal efficacy was noted 1.5 hours before bedtime. Paradoxically, ramelteon marginally, but significantly increased sleep fragmentation and ESS scores compared to the placebo state. Conclusions: Ramelteon is efficacious in maintaining an earlier sleep/wake cycle in adults with ADHD and CRSD but can have paradoxical fragmenting effects on sleep and exacerbate daytime sleepiness. In the presence of a circadian rhythm disorder, the usual dosing and timing parameters for ramelteon need to be carefully considered.

Circadian Disruption and Psychiatric Disorders: The Importance of Entrainment

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CHRONOBIOL INT

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