4 replies to this topic

[Tom_]

I'd be deligted for this to turn into a discussion and think it could be a useful for a lot of members on here suffering with sleeping disorders, affective disorders, cognitive enhancement, geriatric medicine, endocrinologist etc...scarily a lot of people don't even seem to know much about there regulation.

I'll start the discussion with links to a interesting papers (plus the mandatory wiki page) are and then babble on a bit.

http://en.wikipedia....ircadian_rhythm

Pre-clinical Research

http://www.ncbi.nlm....les/PMC3384229/ - Pathophysioloy and pathogenesis of circadian rhythm sleep disorders
http://www.ncbi.nlm....les/PMC3179573/ - Circadian Rhythms and Mood Regulation: Insights from Pre-Clinical Models
http://www.ncbi.nlm....les/PMC3154570/ - Disruption of Circadian Rhythms: A Crucial Factor in the Etiology of Depression
http://www.ncbi.nlm....les/PMC2848671/ - The role of retinal photoreceptors in the regulation of circadian rhythms
http://www.ncbi.nlm....les/PMC3475279/ - Replication of cortisol circadian rhythm: new advances in hydrocortisone replacement therapy
http://www.ncbi.nlm....les/PMC3375033/ - Daily rhythms of the sleep-wake cycle
http://www.ncbi.nlm....les/PMC3104765/ - Circadian rhythms, sleep, and metabolism
http://www.ncbi.nlm....les/PMC3328852/ - Circadian and wakefulness-sleep modulation of cognition in humans
http://www.ncbi.nlm....les/PMC3248591/ - Circadian rhythms of psychomotor vigilance, mood, and sleepiness in the ultra-short sleep/wake protocol
http://www.ncbi.nlm....les/PMC2679862/ - A Clinical Approach to Circadian Rhythm Sleep Disorders
http://www.ncbi.nlm....les/PMC3599978/ - A new chronobiological approach to discriminate between acute and chronic depression using peripheral temperature, rest-activity, and light exposure parameters
http://www.ncbi.nlm....les/PMC3553575/ - Biological rhythms and mood disorders
http://www.ncbi.nlm....les/PMC3569143/ - Circadian Rhythm Characteristics in Mood Disorders: Comparison among Bipolar I Disorder, Bipolar II Disorder and Recurrent Major Depressive Disorder
http://www.ncbi.nlm....les/PMC3354573/ - Neurobiology, Pathophysiology, and Treatment of Melatonin Deficiency and Dysfunction
http://www.ncbi.nlm....les/PMC3196277/ - Impact of Chronic Hypercortisolemia on Affective Processing
http://www.ncbi.nlm....les/PMC2612129/ - CIRCADIAN RHYTHM DISTURBANCES IN DEPRESSION
http://www.ncbi.nlm....les/PMC3119826/ - Sleep Neurobiology from a Clinical Perspective
http://www.ncbi.nlm....les/PMC2812689/ - Good Night and Good Luck: Norepinephrine in Sleep Pharmacology

Clinical Research & near clinical research

http://www.ncbi.nlm....les/PMC3001221/ - A Systematic, Updated Review on the Antidepressant Agomelatine Focusing on its Melatonergic Modulation
http://www.ncbi.nlm....les/PMC2670336/ - Illuminating Rationale and Uses for Light Therapy
http://www.ncbi.nlm....les/PMC3244295/ - Agomelatine
http://www.ncbi.nlm....les/PMC2785860/ - Critical appraisal and update on the clinical utility of agomelatine, a melatonergic agonist, for the treatment of major depressive disease in adults
http://www.ncbi.nlm....les/PMC2899775/ - Agomelatine: The evidence for its place in the treatment of depression
http://www.ncbi.nlm....les/PMC3575211/ - Adjunctive agomelatine therapy in the treatment of acute bipolar II depression: a preliminary open label study
http://www.ncbi.nlm....les/PMC3553570/ - Antidepressant chronotherapeutics for bipolar depression
http://www.ncbi.nlm....les/PMC3181966/ - Hormone treatment of depression
http://www.ncbi.nlm....les/PMC2871175/ - Pharmacology of Ramelteon, a Selective MT₁/MT₂ Receptor Agonist: A Novel Therapeutic Drug for Sleep Disorders
http://www.ncbi.nlm....les/PMC3593297/ - Therapeutic applications of melatonin
http://www.ncbi.nlm....les/PMC2982730/ - The Use of Exogenous Melatonin in Delayed Sleep Phase Disorder: A Meta-analysis
http://www.ncbi.nlm....les/PMC2982726/ - Shedding Light on the Effectiveness of Melatonin for Circadian Rhythm Sleep Disorders
http://www.ncbi.nlm....les/PMC2952772/ - Dose finding of melatonin for chronic idiopathic childhood sleep onset insomnia: an RCT
http://www.ncbi.nlm....les/PMC3079938/ - Light-Induced Changes of the Circadian Clock of Humans: Increasing Duration is More Effective than Increasing Light Intensity
http://www.ncbi.nlm....les/PMC3208844/ - A Randomized Controlled Trial of Cognitive-Behavior Therapy Plus Bright Light Therapy for Adolescent Delayed Sleep Phase Disorder
http://www.ncbi.nlm....les/PMC2647789/ - Efficacy and Safety of 6-Month Nightly Ramelteon Administration in Adults with Chronic Primary Insomnia
http://www.ncbi.nlm....les/PMC3173578/ - Next-Day Effects of Ramelteon (8 mg), Zopiclone (7.5 mg), and Placebo on Highway Driving Performance, Memory Functioning, Psychomotor Performance, and Mood in Healthy Adult Subjects
http://www.ncbi.nlm....les/PMC3304684/ - Bright Light Treatment as Add-On Therapy for Depression in 28 Adolescents: A Randomized Trial

Circadian rhythms obviously have a massive effect on neurological functioning (including psycho-behavioral health). This means there is a wide range of therapeutic applications. The vast majority of the research I have provided focuses on affective disorders and sleep disorders.

More coming...

Edited by Tom_, 25 April 2013 - 07:32 PM.

[stablemind]

Any updates? I'll be testing b12 + BLT to counter excessive daytime sleepiness, but I would also like to know what other options I have. I've been able to deal with mood, focus, memory, etc... but no matter how perfect everything is, sleeping 1.5 hour later than usual wrecks my circadian rhythm and everything goes wack the next day.

[Tom_]

There is some poor evidence that b12 will help to re-regulate Circaidan Rhythems. Not sure what BLT is.

Treating the symptom of escessive daytime sleepiness is rarely the best way to go. In some cases it is entirely nessasy due to no other option - such as in the case of Idiopathic hypersomnia - the disorder can't be cured so management is the only option. Of course that doesn't mean if you have a disease you are working on treating and until then short to medium term management of EDS is not a good idea so you can maintain your functioning e.g a case of atypical depression where you are taking antidepressants/therapy/whatever else and improving but still sleeping if left over 10 hours a day a shortish course of DLPA (you could be using as an AD anyway), Modafinil or other stimulant isn't a reasonable idea.

Also the diagnosis of EDS is also ususally over or under diagnosed due to lack of understanding of the key concept. Extreme, unexplained due to lack of sleep or sedatives which is always debiliting and 'ususally' hard to fight of (i.e. need for frequent napping or sleep attacks) somonlence is the definition. If your sleepiness doesn't meet that then you should be looking into another disorder/symptom and following approiate treatment there.

So in essence if you are sleeping more than 10 hours a day and over the age of 17 then EDS can be diagnosed as a symptom.

Most common disorders are: Depressive disorders (mostly atypical) & ajustment reactions, Primary Hypersomnia & Hypothyroidsm. Find the cause of the exessive sleepiness and treat it at that level.

If your problem after what I've told you is EDS requiring treatment on top you have a few ways to go. DLPA is a good option. Set an alarm an hour before you need to be awake and take 500-1000mg and go back to sleep. Along side the alarm trick if you are reasonably nicotine niave slapping on a patch 1hour to 20 mins before you need to be up can work wonders. Caffine can also play a place. Bright Light Therapy works well espailly if you have messed up circadian rhythems. Sleep hygine is a must and it might not improve the EDS but it sleeping the hour and a half earlier so you can wake up easier then you want to be up can be a bonus. Other stimulant options tend to be Pharm based - at least that I would recommend. Modafinil or Methylphenidate (under the watchful eye of a doctor) are the best and safest options.

If you are suffering from what is more likely a Circadian Rhythem disorder ( you don't need more sleep you just get to sleep and wake up later than is acceptable) then there are a multitude of options. Melatonin or a Melatonergic agonist (Agomelatine for example) taken to make you sleepier earliar can work by itself. A short and I mean short course of low dose Benzo's/Z drugs for between 1 and 2 weeks can force you to fall asleep ealier and taken alongside the melatonin/agonist may more quickly shift your sleep phase. Sleep Hygine is a must and should be practiced at least to a reasonable standard. Bright light therapy can also help move back your sleep phase. During this time you can still be pretty wacked out in the morning and using some DLPA/nictoine/caffine pills when you get up can help but you should only need it for a short while.

If you have MDD or something like that causing the sleep disorder then your best bet is to focus on treating that as best and quickly as you can.

A mix of an antidepressant, melatonin, bright light therapy, sleep hygine and Cognitive Behavioual therapy (online, in a group or 1 to 1) is the way to go. Dealing with the exessive fatigue or in some rarer cases exessive daytime sleepiness can be managed on top with DLPA or Modafinil.

[stablemind]

My excessive day time sleepiness stems from my bipolar 2. This occurs when I experience a shift forward in my circadian rhythm, i.e. sleeping later at night. I'm currently on Seroquel which gets me to sleep every night and helps my BP depression. Adding ginkgo biloba and tryptophan eliminates the depression. Even after treating my depression, my CR still significantly affects me if i experience a phase delay. The next day I experience fatigue, mild depression, memory issues, etc..

I would like to avoid stimulants since they affect my sleep, but I'll try caffeine next time. I would also like to avoid any other antidepressants. Bright Light Therapy (BLT) doesn't seem to help fatigue caused by a CR disruption, but I will try it with B12 to see if it makes me more photosensitive. It does help for Seasonal Affective Disorder on cloudy days.

If I can get to bed before 12 every night then I don't experience these symptoms. Unfortunately due to external factors, there will always be days where I sleep a little later so the best option would be to find something that will help stimulate phase advance when I should be sleeping.

It appears food also influences CR: http://yaledailynews...hm-study-finds/

So basically, melatonin levels and cortisol levels all have a circadian rhythm pattern. Melatonin can be supplemented a few hours before bed to stimulate phase advance.

I'm trying to make a protocol that will prevent a phase delay in CR in the event I have to sleep later than usual.

Few hours before I sleep:
-No eating
-Extended Release Melatonin
-Possibly Phosphatidylserene to suppress elevated cortisol

I'll then force myself to wake up at the usual time, even if it means less sleep. Then start bright light therapy with 3 mg B12 to increase photosensitivity.

Questions:

Have you came across any study that shows cortisol to influence CR?
DLPA have any studies in normalizing circadian rhythms?
What else may impact CR besides what you already mentioned?

Edited by stablemind, 17 August 2013 - 03:56 AM.

[stablemind]

Ramelteon seems to be available in the US so I may give it a try if my protocol fails to work.

In a subsequent trial, a 5-hour phase advance was imposed on 75 healthy adults who were randomized to receive ramelteon 1 mg, 2 mg, 4 mg, 8 mg, or placebo. The subjects were confined in a sleep laboratory under low-intensity light for five nights and six days. Ramelteon 1 mg, 2 mg, and 4 mg produced a significantly greater and more rapid circadian phase advance compared with placebo (−80.9 min, p =0.002; −73.3 min, p =0.003; and 83.4 min, p =0.001, respectively), as indicated by endogenous melatonin secretion offset time; the 8 mg dose showed a phase advance that did not reach statistical significance (−27.9 min, p =0.392) (Richardson et al 2006b).