Chronotherapeutics for Affective Disorders

Little update 3/2/11 - Just found this website with research updates on chronotherapuetics which may be of interest: http://www.chronotherapeutics.org/Index.html
(end little update)

I'm going to spend some more time discussing some nitty gritty, genetics, and biochemistry related to mood disorders (especially), treatments for mood disorders, and circadian rhythm abnormalities.  Bet you can't wait!  In the mean time, however, I came upon some neat articles (1)(2) about the process of chronotherapeutics.  That is, using light therapy, dark therapy, sleep deprivation and sleep phase delay or advance to treat mood disorders, such as depression and bipolar disorder.  A little warning - these methods are powerful, quick, and affect the same neurotransmitter systems as psychiatric medications (more on that in a different post), and it is not a good idea to experiment with these all on your lonesome.  Let me give you a worst case scenario - you try to treat depression with light therapy or sleep deprivation.  Turns out you are bipolar.  You get manic, spend $30,000 on a new stereo system, sleep with your boss, and antagonize your friends and relatives, and end up in a hospital after singing opera naked on your rooftop (this is an invented but not entirely unreasonable scenario).  So... best to let some loved ones know if you attempt these methods, and if you already have a psychiatric diagnosis, don't attempt these methods without the blessing and observation of your therapist or doctor.  In addition, if the methods aren't done quite right, you can very quickly relapse (within 1-2 days). 

Most of you will be familiar with the concept of light therapy.  Sitting in front of special 10,000 lux light sources on late autumn and winter mornings has been proven to be an effective treatment for seasonal affective disorder, major depressive disorders, and even bipolar depression (if you are careful - injudicious use of light therapy can also bring on mania).  The FDA approved lights (such as the ones from this company - this is just the company I typically recommend to patients, I have no relationship to them and receive no monetary or other benefit from them)  all have a 30 day money back guarantee, also, which is nice, and some insurance companies will pay for them if you are lucky.  The usual method is to sit in front of the lights in the morning for 15-30 minutes, glancing at the light every 30 seconds to a minute or so.  You have to do it nearly every day, and it works best if you begin when the seasons change (late September here at 40 degrees north).  Light therapy can nearly instantaneously improve seasonal depression, and I've heard tales of trucks of light therapy boxes driving around to small towns in Alaska and reducing the winter suicide rate along the way. 

But let's get back to the basics of chronotherapeutics.  In general, interventions that lead to sleep phase advance (waking up early and going to sleep early) have an antidepressant effect, and sleep phase delay (going to sleep later and waking up later) will have a depressant (or anti-manic) effect.  Also, reinforcing the natural circadian rhythm will tend to help mental illness - at hospitals in Canada (3) and Italy (4), they noticed that patients in sunny or easterly facing rooms were discharged on average 2&1/2 to 3&1/2 days earlier than patients in rooms without much sunlight. (Even more interestingly, the differences were minimal in the winter, but extended to up to 7 days in the autumn).  Not surprisingly, all of this has been discovered before by our intrepid ancestors.  Classical texts and descriptions of psychiatric wards from 1794 showed that depressed patients were advised to spend time out of doors, and agitated patients were closed up in darkened rooms (5).

One old-fashioned and newly-fashionable method of treating all sorts of depression is sleep deprivation (SD).  There is complete sleep-deprivation, which is self-explanatory, and partial sleep-deprivation,which generally involves waking people up for the second half of the night.  The only known contraindication to sleep deprivation is epilepsy (I've spent some time on the long-term seizure monitoring units in neurology, and we've been known to elicit seizures for diagnosis via EEG by sleep deprivation (basically, sending the medical students and residents - who were up anyway -  to keep the patient awake at all hours) and use of a judicious amount of red wine).  SD's efficacy has been reported in major depression, bipolar disorder, depression in schizophrenia and in Parkinson's disease, and post-partum depression.  Patients who respond best to sleep deprivation are the same patients who respond best to antidepressant medications - those with a diurnal pattern of mood (typically more depressed in the morning and feeling pretty good by afternoon), low IL-6 levels, and an abnormal dexamethasone suppression test.  Light therapy has similarly proved therapeutic (nearly instantly) with depression associated with ADHD, Parkinson's, Alzheimer's, pregnancy, post-natal, and regular depressive disorders.

As with every other method (such as therapy and antidepressants) (except shock therapy, which is up to 90% effective), light therapy and sleep deprivation is at least modestly helpful in 60-70% of cases.  However, and interestingly, people with bipolar depression seem more likely to respond to sleep deprivation or light therapy than to standard antidepressant medications, suggesting to me (and truth be told I've read other papers with other evidence for this theory) that genetic issues with the circadian rhythm system is the primary problem leading to the vulnerability to bipolar disorder.Due to the tricky nature of bipolar depression and the risk of switching to mania with antidepressant drugs, some of the most robust data has been shown for chronotherapeutics (sleep deprivation, phase advance, or light therapy) for this condition, and mood stabilizers (which work upon the circadian rhythm proteins) can enhance and continue the initial benefits brought about via chronotherapeutics.  The medicine remains useful, as once chronotherapeutics are discontinued (one can't be sleep-deprived forever, for example), the depression can return within a hours of a normal night's sleep.  In fact, only 5-10% of the studied bipolar depressed patients remain with a normal mood through  chronotherapeutics alone.  Repeating the intervention doesn't always help, as people tend to become tolerant to the treatment.

One way of ameliorating the tolerance to chronotherapeutic techniques is to combine them.  For example, there is a severely depressed patient with known bipolar disorder in the hospital.  Start with a few days of sleep deprivation, then begin phase advance treatment (going to bed early, waking up early) and morning light therapy to retain the benefits over time.  Perhaps add in some mood stabilizers to enhance the effect (again, I will go into more specifics as to how mood stabilizers and antidepressants affect, directly, the circadian rhythm system in another post - but to give you a preliminary taste, both serum and PET, SPECT, and fmri data has shown that antidepressants and sleep deprivation/phase delay/light therapy affect the same neurotransmitter system in similar areas of the brain), and we have a recipe for nearly immediate reversal of severe bipolar depression with maintenance of normal mood for the foreseeable future.

An interesting part of the discussion of chronotherapeutics is that the techniques (other than the physical lights of light therapy) cannot be patented.  Therefore there is less (short-term) economic motivation for future study (as is the case with most evolutionary medicine ideas).  However, in countries with socialized medicine, far-sighted bureaucrats might see the writing on the wall - cheap interventions (such as sticking all the depressed patients in easterly-facing rooms in the autumn) decreasing hospital times saves real taxpayer money very quickly.  Days in the hospital equals thousands of dollars.  It is that simple.

So if you are depressed, seek light and wakefulness (an old timey depression remedy was to wake up at 3am once a month for those known to be vulnerable to the condition), and if you are manic, seek darkness and low stimuli.  Under close supervision, of course.