Methods for treating circadian rhythm phase disturbances

Abstract

A method for treating circadian rhythm phase disorders is described. The invention provides methods to specifically advance or delay the phase of certain circadian rhythms in humans. The disclosed methods relate to the administration of melatonin at times determined with relation to the time of dim light endogenous melatonin onset. Embodiments capable of alleviating the effects of jet lag, winter depression and shift-work sleep disturbance are,provided.

1 - 43 . (canceled)  
   
   
       44 . A method for achieving a circadian rhythm phase-shifting effect in a human comprising the step of administering an amount of melatonin, a melatonin agonist or compound that increases endogenous production of melatonin in the human, wherein the administered amount of melatonin agonist or compound that increases endogenous production of melatonin in the human is sufficient to achieve a circadian rhythm phase-shifting effect in the human, so that where the circadian rhythm phase-shifting effect is a phase advance, melatonin agonist levels, or endogenous melatonin levels increased by a compound that increases endogenous production of melatonin in the human rise after about CT 6 and before about CT 18, and where the circadian rhythm phase-shifting effect is a phase delay, melatonin agonist levels, or endogenous melatonin levels increased by a compound that increases endogenous production of melatonin in the human rise after about CT 18 and before about CT 6.  
   
   
       45 . A method for achieving a circadian rhythm phase-shifting effect in a human, the method comprising administering to the human an amount of melatonin, a melatonin agonist or compound that increases endogenous production of melatonin in the human, wherein said administration produces in the human a plasma melatonin or agonist concentration of greater than quiescent melatonin or equivalent agonist levels for a time or in a concentration that is different during a time interval from about CT 6 to about CT 18 than that produced during the time interval from about CT 18 to about CT 6, wherein when the circadian rhythm phase-shifting effect is a phase advance, wherein the time interval of greater concentration is between about CT 6 and about CT 18, or when the circadian rhythm phase-shifting effect is a phase delay, wherein the time interval of greater concentration is between about CT 18 and about CT 6.  
   
   
       46 . The method of claims  44  or  45  wherein melatonin, the melatonin agonist or compound that increases endogenous production of melatonin in the human is administered in an immediate release, sustained release or delayed release formulation or combination thereof.  
   
   
       47 . The method of  claim 46  wherein melatonin, the melatonin agonist or compound that increases endogenous production of melatonin in the human is administered at wake-up time, breakfast time, lunchtime, dinnertime or bedtime.  
   
   
       48 . The method of claims  44 ,  45 , or  47  wherein the phase-shifting effect is the adjustment of circadian rhythms into synchrony with local time following transmeridional travel.  
   
   
       49 . The method of claims  44 ,  45 , or  47  wherein the phase-shifting effect is alleviating winter seasonal affective disorder.  
   
   
       50 . The method of claims  44 ,  45 , or  47  wherein the phase-shifting effect is alleviating schedule-related circadian rhythm disorders.  
   
   
       51 . The method of claims  44 ,  45 , or  47  wherein the phase-shifting effect is the adjustment of circadian rhythms into synchrony with the day/night, light/dark cycle in a human having advanced sleep phase disorder.  
   
   
       52 . The method of claims  44 ,  45 , or  47  wherein the phase-shifting effect is the adjustment of circadian rhythms into synchrony with the day/night, light/dark cycle in a human having delayed sleep phase disorder.  
   
   
       53 . The method of claims  44 ,  45 , or  47  wherein the administration time can change from day to day.  
   
   
       54 . The method of claims  44 ,  45 , or  47  optionally including the step of providing bright light at an intensity of about 500 lux to about 100,000 lux.  
   
   
       55 . The method of claims  44 ,  45 , or  47  wherein a pharmaceutical agent is administered to the human that is capable of stimulating melatonin receptors in the suprachiasmatic nuclei of the hypothalamus or elsewhere in the animal to achieve a phase-shifting effect.  
   
   
       56 . The method of claims  44 ,  45 , or  47  optionally including the step of administering to the human an amount of a pharmaceutical agent, said agent being capable of stimulating melatonin receptors in the suprachiasmatic nuclei of the hypothalamus or elsewhere in the animal to achieve a phase-shifting effect.  
   
   
       57 . The method of claims  44 ,  45 , or  47 , the method further comprising the step of regulating exposure of the human to light wherein the human is subjected to reduced light intensity or darkness at a time from about CT 14 to about CT 18, or at a time from about CT 18 to about CT 1.  
   
   
       58 . A method according to  claim 57  wherein the phase-shifting effect is a phase advance, and the human is subjected to reduced light intensity or darkness at a time from about CT 14 to about CT 18  
   
   
       59 . A method according to  claim 57 , wherein the phase-shifting effect is a phase delay, and the human is subjected to reduced light intensity or darkness at a time from about from about CT 18 to about CT 1.