The Diagnosis and Treatment of Circadian Rhythm Disorders

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Adelaide Institute for Sleep Health, Repatriation General Hospital, Daw Park, SA The Diagnosis and Treatment of Circadian Rhythm Disorders Professor Leon Lack School of Psychology, Flinders University Adelaide Institute for Sleep Health Repatriation General Hospital, Daw Park, South Australia

The Circadian World The 24-hour Circadian (Circa=about, dian=a day) physical world (night/day) pervades our society and our bodies. Circadian rhythms are ubiquitous in our bodies. Virtually every physiological, hormonal, biochemical, and behavioural measure taken over time shows a strong circadian rhythm. Circadian rhythms are mainly endogenous and timed by an internal body clock.

Normally Timed Individual Core Temperature Wake Maintenance Zone Sleep? Wake Up Zone Sleep? Sleep Propensity Optimal Sleep Period Circadian Bed Melatonin DLMO Tmin 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 PM Midnight AM Noon TIME

Disorders and Difficulties caused by the mis-timing of the body clock Delayed Sleep Phase Disorder (Sleep onset insomnia) = Timed too late. Advanced Sleep Phase Disorder (Early morning awakening insomnia) = Timed too early Irregular and free-running circadian rhythms = chaotic or drifting later timing Shift Work Disorder = work/rest vs. rhythms Jet-Lag = Rhythm timing catch up

Re-timing the Circadian Rhythm Using Bright Light Considerable research in other species and in humans has established that visual stimulation with bright light is probably the strongest Zeitgeber or circadian re-timer. Dimensions of importance are: Intensity of the light (logarithmic effect) Duration of the light (linear effect) Timing of the pulse re Core Temp. min time Wavelength (colour) of the light

The Body Clock is the SCN Supra-chiasmatic Nucleus

Bright Light Can Re-Time the Body Clock

Melatonin as a Zeitgeber Melatonin is a mild sedative but only during the day when endogenous levels are low. Melatonin also has a chronobiotic or circadian re-timing effect. Melatonin administration is almost the opposite of light, it acts as super darkness. Ingestion of melatonin before normal bedtime can produce phase advances. Ingestion of melatonin late in the normal sleep period causes phase delays.

Melatonin Ingestion Phase Response Curve Phase Advance Bedtime CTmin Phase Delay Lights on, WUT Lights on, WUT

Light and Melatonin are additive but not equal in their circadian rhythm re-timing effects

Delayed Sleep Phase/Sleep Onset Insomnia

Normally Timed Individual 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 PM Midnight AM Noon TIME

Four Hours or more Delayed Rhythm Sleep? Restricted Sleep with forced wake time Tmin Extended sleep with opportunity 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 PM Midnight AM Noon TIME

Chronobiologic Treatment of DSPD With supplementary Cognitive/behaviour Therapy Joe Cool 1mg Melatonin

Advanced Sleep Phase/Early Awakening Insomnia

Hypothesized Three Hour Phase Advance Sleep? 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 PM Midnight AM Noon TIME

Chronobiologic and CBT treatment for ASPD/early awakening insomnia Laura Lark

Irregular Sleep/wake Cycle

Treatment of Irregular Sleep/wake Cycle Target Sleep Period Prescribed Bed Period

Free Running Sleep/wake cycle

Treatment of Free-running Sleep/wake Cycle Target Sleep Period Prescribed Bed Period

Shift Work Sleep Disorder Fatigue on shift, poor daytime sleep Work shift Sleep

Treatment of Shift Work? To treat or not to treat? One or two night shifts should probably not have chronobiologic intervention. Several sequential night shifts can benefit from partial re-entrainment (2-4 hours shift). Bright light on night shift, dark glasses & melatonin in morning (Burgess & Eastman).

Treatment of Shift Work Sleep Disorder based on Burgess & Eastman Core Temp. Min. Work shift Tm Tm Tm Tm Tm Tm Tm

Jet Lag, Destination London Time Jet-lag without intervention could persist 8 days Temp.Min. Westward Plane Flight Heathrow Hotel Intended Nap, not long sleep Very sleepy Very sleepy Very sleepy Very sleepy Sleepy

Destination London Time Jet Lag Minimization, 4 days to adjust Temp.Min. Westward Plane Flight Heathrow Hotel sleepy sleepy sleepy Sleepy

Considerations for Overcoming Jet Lag Number of time zones crossed? East requires phase advances (earlier). West requiring phase delays is quicker. How long the stay in destination? A short stay may not be worth re-entrainment. Adjustments can be made before trip.

Conclusions There are a number of circadian rhythm disorders. These are mainly a result of endogenous rhythms being out of sync with necessary work/sleep time. The endogenous rhythms can be re-timed and brought into sync. The main re-timers are bright light, light avoidance, and melatonin at the appropriate times.