Of course, most physicians prescribe only what the drug companies are pushing, so Ambien (zolpidem) is the most commonly prescribed sleep agent at $82 per month for the 10 mg size (Walgreens, 5/30/04).  It's half-life is 2.6 hours.  Lunesta (Eszopiclone) is a new and slight modification of a very old sleeping pill which will give the company a patent for many years to come with high profits from it's $99 per month cost.  It has an intermediate 6-hour half-life.  Sonata (zaleplon) is another expensive brand-name non-benzodiazepine promoted for insomnia ($85), which has a very short half-life of 1 hour.  Lunesta's "advantage" is that the manufacturer did a 6-month long study which showed continued effectiveness and used the study to receive FDA approval for long-term usage.  In other words, the manufacturer hopes that the patient will be on the medication for the rest of the patient's life.

Ambien causes memory impairment and impaired driving the day after (J Clin Psychopharm 2002;22:576) along with next-day drowsiness for all of these medications.  Lunesta also causes impaired driving in view of its longer half-life.  Auto crashes and fatalities are very likely higher for people taking these.  In a Norwegian police study, 60% of drivers pulled over for suspected drugged driving were driving under the influence of Lunesta's parent molecule, zopiclone.  It is not clear whether these expensive non-benzodiazepine medications, which work in a manner very similar to benzodiazepines, are any less addictive or abuse prone.  The benzodiazepines are much less expensive and do help sleep: temazepam (Restoril), flurazepam (Dalmane), chlordiazepoxide (Librium), clonazepam (Klonopin), lorazepam (Ativan), and others.

I am opposed to using and of these expensive and abuse prone medications for sleep, unless all other options have failed.  They are definitely inferior to melatonin.  Melatonin is natural and not addictive; it causes daytime alertness, not drowisness; and it is a great anti-oxidant associated with increased longevity, reduces the risk of Alzheimer's, and is very good at reducing stroke damage in several animal models.  Melatonin is a great anti-oxidant and likely to improve memory in older individuals.  Melatonin is produced in the pineal gland in the middle of the human brain.  Finally, melatonin is available without a prescription for just $3-4 per month.  For numerous studies and research, see melatonin.  

The Japanese drug company Takeda has come out with an expensive ($80/month) melatonin receptor agonist named Rozerem (ramelteon).  There is no evidence that it is better than melatonin, the benefits on amount of sleep are minor, and its side-effects are sleepiness, dizziness, nausea, fatigue, headache, insomnia, and an elevated prolactin level in 32% of patients.  This high prolactin could lead to infertility, decreased libido, and osteoporosis.

Lunesta (eszopiclone) is a drug company relaunch of an old medication whose patent protection has expired.  Zopiclone has been used in Europe of 20 years as an addictive sleep remedy.  The drug company used a favorite trick of separating out the active isomer from the original medication and selling it as a new medication.  There is absolutely no evidence that the new Lunesta, a knock-off of the original Imovane, is any better than the parent medication.  In fact, it is exactly the same active ingredient without the inactive mirror image but with some other inactive ingredients.  Governmental officials, always looking for campaign contributions, are happy to consider the ruse as a new medication and sock it to the taxpayer.  After all, it's not their money.

Eszopiclone (Lunesta) Said Helpful in 6 Month DB: In a 6-month DB PC study of 788 adults ages 21 to 69 with primary insomnia with, on average, less than six-and-a-half hours of sleep per night, or it took at least 30 minutes to fall asleep for at least one month, the 3 mg dosage was helpful throughout the study. Eszopiclone is non-benzodiazepine cyclopyrrolone. The abstract only reports that the medicine was more effective than placebo without giving the actual benefit. Andrew Krystal, et al. Duke. Sleep 2003 Nov 1;26(7):793-9.

Eszopiclone Helped Elderly in Short Study: A PC DB 2 week study with 231 elderly ages 65-85 reports that total sleep time increased 40 minutes with the quality and depth of sleep improving significantly (p<.001). Daytime napping was 2 hours less with the 1 mg dose and 2 1/2 hours less with the 2 mg dose. Alertness and well-being improved as well.  8/21/03. Cincinnati. David Seiden et al. Eszopiclone Rapidly Induced Sleep and Provided Sleep Maintenance in Elderly Patients with Chronic Insomnia. 11th Interntl Congress, Internatl Psychogeriatric Assoc, Chicago, IL. Sepracor

Melatonin as Good or Better than Zolpidem (Ambien) Sleeping Pill and Without Memory or Performance Impairment: In a DB PC study of 80 adults after a good night's sleep, zolpidem (Ambien) 0, 5, 10, or 20 mg was given at 10:00 am and then oral melatonin 0 or 5 mg at 10:30 am (thus, n = 10 per drug combination). Subjects napped from 10:00 am to 11:30 am, at which time they were awakened for cognitive tests. A second nap ensued from 12:45 pm to 4:00 pm, followed by further testing. Melatonin 5 mg plus zolpidem 0 mg enhanced daytime sleep (P < .05) with no memory or performance impairment (P > .05). Zolpidem 20 mg plus melatonin 0 mg also enhanced daytime sleep nonsignificantly, but memory and vigilance were impaired (P < .05). Melatonin's sleep-promoting effects were not evident until the second nap. Daytime sleep and performance following a zolpidem and melatonin cocktail. Wesensten NJ, Balkin TJ, et al. Walter Reed. Sleep. 2005 Jan 1;28(1):93-103. 

Melatonin Did Well Compared to Addictive Sonata, Restoril or Lunesta Parent in DB: Nine men and 14 women, ages 21-53, were assessed for psychomotor performance before and for 7 hours after taking a single dose of placebo, zaleplon (Sonata) 10 mg, zopiclone (similar to Lunesta) 7.5 mg, temazepam (Restoril) 15 mg, or time-released melatonin 6 mg in a double-blind crossover study with counterbalanced treatment order. More sleep, shorter sleep latency, and more drowsiness occurred immediately after psychomotor testing compared to before testing for all medications. Melatonin did not cause any sleep prior to psychomotor testing sessions, but caused sleep and reduced sleep latency after psychomotor test sessions from 1 3/4 h to 4 3/4 h post-ingestion. The sleep-inducing power of the medications before psychomotor testing was zopiclone > zaleplon > melatonin > temazepam. The corresponding effect after psychomotor testing was zopiclone > melatonin > zaleplon > temazepam. Sleep-inducing pharmaceuticals: a comparison of melatonin, zaleplon, zopiclone, and temazepam. Paul MA, Gray G, MacLellan M, Pigeau RA. North York, Ontario. Aviat Space Environ Med. 2004 Jun;75(6):512-9

Melatonin Does Just as Well in Single Dose as Lunesta Parent in DB: In a DB crossover study of 30 aircrew flying 3 transatlantic missions over which they took each of the 3 medications (placebo, sustained-release melatonin 2 mg, or zopiclone 5 mg), the results of the actigraphic data show that relative to placebo, aircrew on melatonin and zopiclone fell asleep more quickly (melatonin: p < 0.01, zopiclone: p < 0.003), slept more (melatonin: p < 0.02, zopiclone: p < 0.005), had fewer awakenings after sleep onset (melatonin: p < 0.004, zopiclone: p < 0.01), and spent less time awake after sleep onset (melatonin: p < 0.01, zopiclone: p < 0.05). The results of the questionnaire data show that relative to placebo, aircrew on melatonin and zopiclone experienced less difficulty getting to sleep (melatonin: p < 0.0001, zopiclone: p < 0.001), had fewer awakenings (melatonin: p < 0.005, zopiclone: p < 0.001), less difficulty returning to sleep after awakening (melatonin: p < 0.0001, zopiclone: p < 0.0001), and reported a better sleep quality (melatonin: p < 0.0003, zopiclone: p < 0.0004). There were no statistically significant differences between melatonin and zopiclone in any of the actigraphic or questionnaire sleep parameters. Melatonin and zopiclone as facilitators of early circadian sleep in operational air transport crews. Paul MA, Gray G, Sardana TM, Pigeau RA. North York, Ontario, Canada. Aviat Space Environ Med. 2004 May;75(5):439-43. Ed: Zopiclone (Imovane) is a somewhat addictive hypnotic medication popular in Europe as a sleeping remedy.  A Norwegian study found 60% of 100 drivers stopped under suspicion of being drugged drivers tested positive for elevated levels of zopiclone. 

Pre-operative Sedation: Melatonin as Good as Addictive Benzodiazepine: In a 66-patient DB PC study of patients undergoing laparoscopic cholecystectomy, those given melatonin 5 mg or midazolam 15 mg 90 min before anesthesia, sublingually, had a significant increase in sedation and decrease in anxiety before operation compared with placebo. After operation, there was no difference in sedation scores of all groups. There were no significant differences among the groups in terms of neuropsychological performance after the operation. Amnesia was notable only in the midazolam group for one preoperative event. Perioperative effects of melatonin and midazolam premedication on sedation, orientation, anxiety scores and psychomotor performance. Acil M, Basgul E, et al. Hacettepe University, Ankara, Turkey. Eur J Anaesthesiol. 2004 Jul;21(7):553-7

Non-Addictive Melatonin as Good as Addictive Midazolam for Pre-Laparoscopy Anxiety and Sedation in DB: In a DB PC study of 66 patients undergoing laparoscopic cholecystectomy, patients were given melatonin 5 mg, midazolam 15 mg or placebo, 90 min before anaesthesia, sublingually. Patients who received premedication with either melatonin or midazolam had a significant increase in sedation and decrease in anxiety before operation compared with controls. Perioperative effects of melatonin and midazolam premedication on sedation, orientation, anxiety scores and psychomotor performance. Acil M, Basgul E, Celiker V, Karagoz AH, Demir B, Aypar U.Hacettepe University, Ankara, Turkey. Eur J Anaesthesiol. 2004 Jul;21(7):553-7 

Thomas E. Radecki, M.D., J.D.

modern-psychiatry.com

Email: [email protected]