Time-Shifting Medicines

Types of Chronobiotics

A number of melatonin agonists have been approved for use or are in various phases of clinical trials. An agonist is a substance that mimics the body’s own regulatory function, by binding to the cell receptor and stimulating normal function. Since melatonin has a short half-life, scientists have developed prolonged release formulations to provide melatonin throughout the sleep period to maintain sleep throughout the night. The melatonin agonists sold for clinical use tend to have a longer half-life than melatonin. All of the following medications have shown to be effective in improving sleep quality.

Ramelteon (brand name Rozerem) has been approved by the Food and Drug Administration for use in the United States. Ramelteon reduces the amount of time needed to fall asleep and increases the length of sleep, and is especially effective for treating insomnia in the elderly. There appears to be no influence on balance, mobility or memory. Side effects are mild; and ramelteon has no effect on alertness, there is no “hangover,” and no withdrawal symptoms. Ramelteon is the most notable and successful chronobiotic to date aside from melatonin.

Tasimelteon (brand name Hertlioz) has been approved by the FDA for treating blind people with circadian sleep disorders. Trials have shown it to be useful in treating delayed sleep phase syndrome (falling asleep and waking too late) and advanced sleep phase syndrome (falling asleep and waking too early). Tasimelteon is not "labeled" for these disorders, meaning the FDA has not explicitly approved the drug for treating the disorders. But doctors may use their judgment to prescribe the medicine if they feel it is warranted. Made by the drug company Vanda, the medicine appears to work in a manner similar to that of ramelteon.

Agomelatine (brand name Valdoxan) is an antidepressant sold in Europe and Australia but not in the United States. Agomelatine improves sleep in people with depression; this then improves the depression symptoms. Like other some other chronobiotics, agomelatine is a melatonergic receptor agonist. It also has "antagonistic activity at type 2C serotonin (5-HT2C) receptors". like other drugs that are anxiolytic (anti-anxiety) medicines. This drug is effective for the treatment of SAD and may also be useful in treating seasonal weight gain. Agomelatine is tolerated well, with no behavioral changes, no dependence, and no “hangover.” Agomelatine needs safety studies to determine the effect of its use over a long period of time. (Agomelatine has been used as an example of how some new medicines are subject to publication bias - where the promoters punish only positive test results and do not publish ones that show the drug has little or no benefit.)

Circadin ™ (prolonged-release melatonin 2 mg) has been approved by the European Medicines Agency for the treatment of insomnia. Melatonin is released over a period of 8 to 10 hours, and is used for the short-term treatment of insomnia in people 55 years and older.

Non Melatonin Agonists

Lithium, which is used to control bipolar disorder, seems to lengthen the intrinsic period of the pacemaker in the SCN. The antipsychotic haloperidol affects the sleep/wake cycle and could be classified as a chronobiotic. Beta blockers, used to treat hypertension, are known to affect the pineal gland and suppress release of melatonin into the bloodstream.

Alteril™, Melatrol™, Restaid™, and Somulin™ are just a few of the 150 sleep aids available over-the-counter; these preparations contain adequate and safe amounts of natural ingredients that are associated with sleep-promotion. Always check with your doctor before adding a sleep-aid, especially if you have other medical conditions or are taking prescription medications.

Vitamin B12 has been proposed as a chronobiotic as have some psychotropic drugs.

Theophylline and pentobarbital are sometimes considered chronobiotics, although these are not often used these days due to side effects. In the past theophylline was used for respiratory diseases, while pentobarbital is an old-style sleeping pill, not mainly used for treatment of seizures. The steroid dexamethasone, often used for arthritis, also has chronobiotic properties..

Article: Toward a classification of medications for sleep and circadian rhythm disorders


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