okay well welcome to another MedCram lecture we talked in the last edition of
behavioral therapy for insomnia we went over relaxation technique sleep
restriction therapy cognitive therapy and cognitive behavioral therapy what
we're gonna talk about next is the part that everybody thinks about when we talk
about insomnia and that's sleeping pills medications now there's four different
classes of medications there's the benzodiazepines
there's the non benzodiazepine sedatives there's the melatonin agonists and then
finally the antidepressants now medications in general do usually
improve daytime function they have better quality of life there are a few
comorbidities but you've got to consider that in general especially the
benzodiazepines that there are side-effects of addiction with time
long-term use and also the longer you use a sleeping pill the less likely it
is to do the job that you intended it to do in the first place you have more
tolerance to these medications so in what type of patients would these risks
go up well in pregnancy you have an increased risk of fetal malformations
also if there's alcohol consumption going on at the same time and kidney
liver or lung disease certainly if the patient has sleep apnea giving them a
sleeping pill could make the sleep apnea worse you really want to be careful in
nighttime decision makers so people who are on the job people who are watching
alarms things of that nature and finally the elderly people who are
75 years plus so this is a busy slide but let's go through this methodically
so we've got medications there's four different classes of medications let's
talk about the first two classes that benzodiazepines and the non
benzodiazepines so these non benzodiazepines are very similar to the
benzodiazepines but they have a different chemical structure as will
show you the benzodiazepines in general and we're talking about like try acilam
and some of these drugs like pro some ativan rest ruled al main Doral these
all bind - the gaba-a receptors okay and they're
long-acting they decrease the sleep latency that's the amount of time it
takes to fall asleep so they do their job there but they also increase that
second type of sleep that second sleep phase not REM not n3 but stage two sleep
they also increase total sleep time so that is intuitive they decrease REM
that's a very interesting characteristic because in patients with REM behavior
sleep disorder where REM sleep seems to be the problem these benzos actually
help now these benzos can cause amnesia and
so you have to be aware that they do impair memory they decrease anxiety
they've also been used as anticonvulsants as you know ativan is a
great anticonvulsant some of the side effects include daytime sleepiness motor
and cognitive problems with dependence and then complex sleep related behaviors
what I mean by that I mean sleep sex sleep eating sleepwalking there's been
many lawsuits associated with of people with automatic behavior at night that is
related to benzodiazepines when we look over at the cousins of the
benzodiazepines which are the non benzodiazepines and I've got some of
their structures down here so this is the benzodiazepine structure generally
speaking and this is a couple of the other ones this is zolpidem that's a non
benzodiazepine this is gsella plon and then finally is
okhla clone which is the same as lunesta these three are different in structure
to the benzodiazepine that's why they're called the non benzodiazepines but these
are the probably the ones that you're familiar with
there's ambien sonata and lunesta so these also target the gaba-a receptors
but they're more specific they're cleaner they do decrease sleep latency
they do increase stage two just like their benzodiazepine counterparts as
well as increased total sleep time reduce REM and impaired memory however
they seem to cause less decrease in anxiety and they're less of an
anticonvulsant because of their specificity in terms of side
FEX we see less of the side-effects that we do with the regular benzos
such as less daytime sleepiness less problems with motor less problems with
cognitive behavioral problems less dependence and less complex sleep
related behaviors now the other thing that's important is looking at the half
life which I have listed here the half life is important because if you take a
long-acting sleep medication and you wake up
eight hours later you could still have this medication hanging around so it's
important to know the half-life of these medications so ambiens got a half-life
of two hours ambien cr also two hours sonata is pretty short in fact it's the
shortest it's about one hour the way I remember that is a a sonata it last
about as long as a sonata maybe a little bit longer and then finally lunesta it's
very slow it's longer acting and I just think of a slow-moving butterfly yeah if
you will so those are the characteristics of both the benzos and
the non benzos what I would remember there is that they're both potentially
causes of dependence so be aware of that but the non benzos are probably cleaner
in terms of sleep medication now recently this came out in 2013 you
should probably know about this the FDA which has approved the use of ambien
ambien cr agilar and Zilpah mists have been FDA approved for for sleep but they
were looking at new data and blood levels in some patients may be high
enough the morning after use to impair activities so again they're sensitive to
these long-acting drugs that can cause high levels of sleep medication in the
patient's blood when they're supposed to be getting up and so as a result of that
they recommended lowering the dose specifically in elderly patients now
specifically the FDA warning that occurred in January of 2013 for zolpidem
recommended the use of a lower dose in women than previously recommended and
also considering this in men as well and of course the ambien cr recomm
was a lower dose and the quote was here that patient should not drive her engage
in other activities that require complete mental alertness the day after
taking zolpidem extended release because zolpidem levels can remain high enough
the next day to impair these activities so if this is something you want to take
on a daily basis if you read their recommendation you pretty much shouldn't
be driving so you've got to be aware of these FDA warnings okay so let's move on
we've talked about one and two number three is the melatonin agonists well
there's only one in that category and that's Rimmel taun rose Ihram and this
is a melatonin agonist it binds to M receptors tighter than melatonin does
actually pretty short acting and because melatonin is used in sleep onset this
medication rose M is actually good for sleep onset insomnia so if the patient
has trouble getting to sleep but has no trouble staying asleep this might be a
good medication for them there are fewer side effects than there are with benzos
or non benzos and there's no hypnotic problems symptoms the next day now this
is the key point it's not habit-forming so it is not a dependent medication so
if you're concerned about a patient becoming addicted to sleep medication
this might be the medication for them now it can increase prolactin and
decrease testosterone levels however the FDA does not at this point see the need
to monitor so this is another medication that may be beneficial again the
antidepressants is the last category we look at things like doxepin
amitriptyline and trazadone and this is what I would say if you've got a patient
who's depressed and they're also having problems with sleep fine go ahead and
pick an antidepressant that also treats insomnia but I wouldn't go to an
antidepressant as a first-line agent if the patient does not have a psychiatric
illness so these are kind of twofers so doxepin is fda-approved but things like
amitriptyline and trazadone these are probably not the first-line drugs I
would go to unless the patient also was depressed so if you look at
some of these studies here trazadone versus zolpidem there was really no
difference so why don't we go with the one that's actually fda-approved for
insomnia and basically the sleep societies don't recommend the use of
sedating antidepressants if the patient doesn't have a psychiatric illness
already so generally speaking I would stay away from antidepressants unless
there's another reason to choose them some of the things that are commonly
used that are not recommended in terms of the state of the science conference
that was done benadryl this is particularly not good in elderly
as it causes a decrease in alertness cognitive function and increases dry
mouth antipsychotics there's only a few trials looking at this and many side
effects barbiturates again a few trials and many side effects some of the things
that are done over the counter like valerian melatonin and alcohol we've
already talked about alcohol they can actually promote sleep disturbance later
in the night because of its short acting nature melatonin is not FDA approved in
fact it's not even regulated it's a nutritional supplement so it can be used
in sleep phase delay syndromes and usually it's a lower dose that's going
to help but again resume I think is the medication that probably would work
better valerian does decrease sleep latency by
less than a minute no regulation once again so you don't know how much
valerian you're actually buying when you think you're buying valerian it's not
regulated so again the sleep societies do not recommend it a couple issues
about side effects and older adults we talked about increase in sleep quality
increase in total sleep time decrease frequent awakening however there is
about a two to five time adverse cognitive or psychomotor event so we got
Falls we get fractures and that goes up interestingly they did a study not too
long ago that showed that mortality went up now this was an observational study
this was not a randomized placebo-controlled trial so the evidence
is not as strong but it was very concerning that observational studies
connected sedative and all cause mortality to as high as an
odds ratio of 4.5 so this still needs prospective study data to look at it to
see if there's actually causation as opposed to just association okay so what
do we talked about patient with insomnia they come into the office we look for
diseases that are easy to rule out we do hygiene and stimulus therapy and if that
still doesn't work then we go down the road to behavioral therapy and selected
medication which one do we do first in terms of behavioral therapy and
medication do we do them at the same time that we do one and then the other
what does the data say join us for the next lecture where we get into that
issue
you