Hypnotics: Sleeping Pills, Part 2

In this section we will review some of the common and a few of the less common hypnotics (sleeping medications) and distinguishing characteristics.  I am going to break the medications down by pharmacologic class to make it easier and clearer, at least easier and clearer for me if not for the reader. 

First, we should start with alcohol (ethyl alcohol).  This drug has been widely available for millenia and since the invention of doctors, there have been doctors using alcohol as a medicine for their patients for sleep.  And for worms.  And for cankers.  And for scalp lice.  And for fever. And for pustules.  And for rat bites.  Alcohol is sedating.  It can promote sleep if given in large enough quantities.  However,  there is initially has reduced REM sleep followed by REM rebound and vivid dreams.  Sleep becomes fragmented by awakenings and is poorly restful.  Often people complain of insomnia.  Interestingly, the effects of alcohol on sleep can last hours after ingestion so that several drinks in the afternoon can cause insomnia for some people that night.  Furthermore, heavy alcohol users can have sleep disruption months after discontinuing alcohol.  Although alcohol is a fundamental component of social interaction and culinary preferences for many, it is best if it is not used pharmacologically and like most products, it should be avoided when side effects occur. 

Melatonin:  Take the hormone of the pineal gland and you have melatonin.  If you don't know where your pineal gland is, please stop guessing!  Some of you were just wrong.  Some of you were guessing in places I would rather not think about.  The pineal gland is in the brain.  It secretes melatonin.  It seems to do this to tell our brains that it is dark and we should go to sleep.  The eyes tell the hypothalamus which tells the pineal gland.  It is a mild but very useful effect to coax us to sleepy-land.  I suspect that when we were living in smaller hunter-gatherer groups it was much more useful to have a hormone that made hunter-gatherer me drowsy at night so I would tend to want to lay down and sleep rather than run around willy-nilly in the dark where I could trip and break something (no E.R. with orthopedic surgeon on call) or get eaten by something nocturnal.  Taking exogenous (pill) melatonin can be quite useful in three circumstances:  a) Jet Lag: take 1 hour before bedtime at your new time throughout your trip and for 1-2 weeks when you return.  b) Shift Work: take 1 hour before bedtime during day sleep.  c) Chronic Insomnia:  take 60-90 min before bedtime nightly.  Melatonin is generally considered to have relatively few side effects.  However, one major side effect is vivid dreams or nightmares.  If this side effect occurs and continues, you can try to cut down on the dose or stop and restart the medicine.  However, is is very likely that the side effect will return every time you take it. 

Barbiturates:  This class of medications is highly sedating and is very potent to induce sleep.  However, these medications are hardly ever used as sleeping medications due to the abuse potential and safety issues they carry.  Instead, they are now used primarily as anti-seizure medicines and anesthesia medications.  Examples include:  Secobarbital (Seconal), Pentobarbital (Nembutal - used for animal euthanasia, treatment of seizures, capital punishment, physician-assisted suicide), Butalbital (Fiorinal - migraine treatment), Phenobarbital (seizure treatment), among several others.  Getting good sleep is important, but it will never be so important that patients should take a couple of the capital punishment pills to get to sleep. 

Benzodiazepines:  This is a large class of medicines some of which are used for sleep, others are used for other purposes.  It ranges from the very short acting intravenous Midazolam which you are likely to receive when you have a procedure like a colonoscopy.  It is sedating and it affects the memory so that you stay comfortably resting and you wake up not remembering anything about the procedure, which is the best way to have a colonoscopy. When the colonoscopy is done, the medicine is wearing off.  On the other end of the spectrum is a medicine like valium.  It is a mildly sedating medicine which primarily works to blunt anxiety.  It works for many hours and it has active metabolic products that last more than 24 hours.  The purpose is a long, low level effect to blunt revved up anxiety.  In the middle of the spectrum are many medicines.  Some with more sedation effects and some with more anxiety reduction, each with their varying durations of effect.  The following are a list of medicines sometimes used to promote sleep.  Some are used to promote sleep when other conditions are present.  If these medications have been used regularly at higher doses, a taper should be used to come down off of the medicine. 
Triazolam (Halcion) 0.125 - 0.25 mg
Clonazepam (Klonopin) 0.25 - 1 mg
Lorazepam (Ativan) 0.25 - 1 mg
Alprazolam (Xanax) 0.25 -1 mg


BZRA's (Benzodiazepine Receptor Agonists) Think of this group as Ambien and its cousins.  You have got to give the pharmaceutical companies credit.  They came up with a great one.  Barbiturates are addictive and dangerous.  Benzodiazepines have long half-lives and other effects on the brain besides just sleep like affecting anxiety, mood, etc.  These scientists made a much more pure sleeping-only pill.  Unlike its predecessors it starts to work in 20 minutes, not 45 to an hour.  It wears off reliably in 6 hours.  They had a brilliant pill.  And they sold millions.  If it's so great why haven't we cured insomnia? The answer, as you might have guessed, is that pills do not solve complicated problems like insomnia.  Sleep hygiene (see subsequent blog post) is critical for good sleep.  Other health issues can get in the way.  Feeling sick while undergoing chemotherapy, worrying about one's business but feeling too sick to go to work, realizing that everything that was worked for is dissolving like that soggy cake in the annoying seventies song all can prevent sleep, ambien or not.  Then medical professionals need to step in.  Sleep professionals have specific training in these matters. 
Side effects and precautions:  There are many, but they occur infrequently. 
Side effects of these medicines:  temporary memory loss, sleep walking, sleep eating, there have been reports of sleep driving,
Precautions:  Notify living partners (adults) that you are taking a sleeping pill tonight.  If you seem to be walking in your sleep, they should verbally encourage you to return to bed.  If you seem to be doing something that you shouldn't, such as going outside in your pajamas in the rain at 3 a.m., they should direct you back to bed. After taking your sleeping pill, do not use the internet.  Ambien works quickly and you may not be thinking clearly when you make a purchase or send an email.  To your boss.  Calling him a name that describes the posterior portion of a donkey.

Currently available BZRA's are:
Zolpidem (Ambien) 2.5 - 10 mg
Escitalopram (Lunesta) 1-3 mg
Zolpidem (Ambien CR) 6.25 - 12.5 mg
Zaleplon (Sonata) 5-10 mg




Meltatonin receptor agonist:  Ramelteon (Rozerem) is the only currently available medication in its class. It can be effective in some patients with insomnia.  It is most beneficial after the patient has been using the medication for at least 1-2 weeks.  Side effects are limited.  There are some drug interactions that need to be checked with each prescription of Ramelteon.