YOU MAY BELIEVE YOU ARE SLAVE TO THE CLOCK – IT WAKES YOU UP AND TELLS YOU WHEN TO BE AT WORK, RETURN HOME, HAVE LUNCH, MEET THE FAMILY AND SO ON. BUT THERE IS ANOTHER CLOCK LYING IN YOUR BRAIN WHICH HAS MUCH MORE INFLUENCE OVER YOUR BODY AND MIND THAN YOU MAY REALISE
HOW TO PRACTICE MEDICINE WITH MORE RHYTHM
CIRCADIAN RHYTHMS AND TREATMENT
RAJ PERSAUD FRCPsych CONSULTANT PSYCHIATRIST
Take two tablets and call me in the morning, used to be the wily doctor’s familiar mantra. Unbeknownst to most of us, the latest research suggests this old saying reveals an implicit understanding that circadian rhythms could have a useful impact on our out of hours call outs!
Is it possible that a bit of basic psychology is in play here? Namely that patients who are not that physically ill may often feel better in the morning, after our reassuring words, and are less likely to report to us feeling unwell after a good nights sleep?
I have long had an interest in circadian rhythms and their impact on medicine in general, and psychiatry in particular. The word circadian has linguistic roots referring to ‘about a day’ and refers to the 24 hour cycle that much of our bodily processes follow. The internal clock regulating our body’s various physiological processes resides in the Suprachiasmatic Nucleus, in the Hypothalamus part of the Brain. This small area of only around 20,000 cells instructs the Pineal Gland to secrete Melatonin on a 24 hour cycle and this hormone appears to be the ‘grand conductor’ of various other clocks and processes in our body.
I remain intrigued at how little most doctors are aware of the numerous advances in the area of Chronobiology – the discipline devoted to the study of biological rhythms in the body. Increasingly knowledge of the circadian rhythms is making contributions that could have an impact on our daily practice, no matter what branch of medicine you happen to be in.
For example, recently Melatonin has been associated with anti-cancer properties, perhaps linked to the fact cell division in our bodies follows circadian rhythms.
Another series of intriguing examples have been reviewed by Asim Sattwa Mandal and colleagues at the Department of Pharmaceutical Technology, Jadavpur University, in West Bengal, India, who have recently produced a fascinating over view of the latest circadian rhythm disease findings in Chronobiology. In their paper, published in the Journal of Controlled Release, they point out that several well known medical disorders, symptoms and much psychopathology, all involve circadian rhythms.
As a result, they contend that drug delivery systems in the future, and indeed therapeutic interventions more generally, might significantly benefit from being more attuned to circadian rhythms. What this means is more precision over exactly when a treatment is delivered, could make a big difference in the outcomes for patients over a wide spectrum of disorders.
In their paper entitled ‘Drug delivery system based on chronobiology—A review’ they marshal a gamut of fascinating data in support of their contention that disease in the future must be treated with more regard to circadian patterns. For example, they point out that the elevation of body temperature in fevers follows circadian rhythms, and these vary, intriguingly, depending on the type of infection. For example, fever due to bacterial infections is higher in the evening, while that due to viral infections, tend to be more elevated in the morning. This of course is a group effect so don’t go diagnosing purely on when your patient reports the peak in temperature!
They also point to other research which found that Duodenal perforations reveal highest incidence in the afternoon, while gastric perforations show a major peak around noon, and a secondary peak near midnight. For Duodenal ulcer perforation, there is also significantly higher incidence in May to July and in November to December. There is also a significantly higher incidence on Thursdays and Fridays, as compared to Sundays through to Mondays – for reasons that remain unclear.
Their review also found that allergic rhinitis symptoms such as sneezing, occur most frequently in the morning, and least frequently in the middle of the day. Patients with osteoarthritis tend to have less pain in the morning, and more at night. While patients with rheumatoid arthritis have pain that usually peaks in the morning, and decreases throughout day.
Moving on to the implications for treatment, and in particular to timing of drug delivery, they quote animal research which finds the survival rate of those suffering acute lymphoblastic leukemia dosed with combination of 6-mercaptopurine and methotrexate was double in the evening, compared to morning dosing. One possible mechanism in circadian rhythms involving treatment of cancer is another finding involving circadian fluctuation in blood flow at tumor sites. Tumor blood flow at night has been found to be considerably higher than during daytime.
Treatments in depression and psychiatry more generally may also benefit from being more attuned to the fact that various psychological processes, as well as biological ones, follow circadian rhythms. For example, mood generally peaks around 11am in the morning. This means this might be a good time to ask, for example, for a pay rise!
Though if you work in the NHS, no time is ever a good time.
Dr Raj Persaud FRCPsych is a Consultant Psychiatrist working in Private Practice at 10 Harley St and in Surrey.
Drug delivery system based on chronobiology—A review Review Article
Journal of Controlled Release, Volume 147, Issue 3, 1 November 2010, Pages 314-325
Asim Sattwa Mandal, Nikhil Biswas, Kazi Masud Karim, Arijit Guha, Sugata Chatterjee, Mamata Behera, Ketousetuo Kuotsu
Declaration of Interest: Dr Persaud has been invited to talk at meetings organized by the pharmaceutical company Servier, to lecture on circadian rhythms in medicine.