The Corpus Callosum

href="http://en.wikipedia.org/wiki/Image:Amitriptyline-2D-skeletal.png">i-5b09d0f0ff0748f0d6a8ee7be38af01d-200px-Amitriptyline-2D-skeletal.png face="Helvetica, Arial, sans-serif">This post is
about amitriptyline, one of the oldest
antidepressants on the market in the USA.  It also used to be
the
most widely-prescribed antidepressant.

I’ve decided to not attempt an encyclopedic style of description of the
pharmacological action of the individual antidepressants.
 That is
readily available already at Wikipedia, among others.  But in
order to fully understand the topic, those who are not familiar with
the pharmacology should probably go to the general statement about
tricyclic
antidepressants
in Wikipedia and read that for background,
then the specific article about href="http://en.wikipedia.org/wiki/Amitriptyline" rel="tag">amitriptyline.
 (Amitriptyline is a member of the family of antidepressants
known as tricyclics.)  

Also, you might want to read the more abstract posts I wrote on the
topic of selection of antidepressants.  They can be found by
clicking on the Category link in the sidebar for antidepressants.

What I am going to write about are the tidbits of information that I
think are important, or interesting, but that are not likely to be
found in a standard reference.


Why
was amitriptyline the most widely prescribed antidepressant, before
Prozac came along?  First, it is important to realize that
most prescriptions for antidepressants are not written by
psychiatrists.  Most are written by primary care
practitioners.  Second, amitriptyline has numerous href="http://en.wikipedia.org/wiki/Off-label_use">off-label
uses.  That is, it is good for many things other
than the treatment of depression.  Probably a lot of those
prescriptions were written off-label, with the drug being used as a
nonaddictive sleeping pill.  25-50mg will help most people get
to sleep pretty well.  Also, the drug is used to treat pain,
particularly href="http://www.clevelandclinic.org/health/health-info/docs/3600/3687.asp?index=12094">neuropathic
pain, or migraine.  It also is used to treat href="http://www.mayoclinic.com/health/fibromyalgia/DS00079"
rel="tag">fibromyalgia pain, stress urinary
incontinence, and a few other things.

Amitriptyline was never a favorite among psychiatrists, primarily
because of the fact that it has an adverse effect burden higher than
that of most antidepressants. It may be that the many non-psychiatric
uses led primary care practitioners to become familiar with
amitriptyline, so when they went to prescribe an antidepressant, they
tended to prescribe it instead of one of the others.  

So when would it be a good idea to use amitriptyline for treatment of
depression?  The short answer is that it is not, unless the
patient has a prior history of a good response to the drug, or unless
many others have been tried, and your are working your way down the
list.  

The long answer is a bit more complicated.  Sometimes, it
makes sense to prescribe an antidepressant when it has a side effect
that is desirable; for example: sedation, urinary retention, or
constipation.  If a patient has both depression and migraine,
or depression and neuropathic pain, it might make sense to use one drug
instead of two.  Or, if a person has a partial response to
another drug, say, sertraline, but has not attained href="http://www.medscape.com/viewarticle/462850">remission,
it might make sense to add a little bit of a tricyclic antidepressant
to augment the response.  

In general, it would not be a good idea to try to use amitriptyline as
a single agent to treat depression plus pain.  The reason is
that that the pain often can be managed by low doses of amitriptyline
(10-50mg), doses that are too low to have much effect on depression.
 The effect is not lost at higher doses, but in general, you
do not get better analgesia with higher doses, but you do get more
undesirable adverse effects.  In order to have a decent chance
of treating depression, you have to use higher doses, often in the
100-200mg per day range.

One situation in which I might use amitriptyline is in cases where
people have a partial response to an SSRI, but may also have a side
effect to the SSRI such as insomnia or diarrhea.  Adding
10-25mg of amitriptyline might make sense in that context.
 Something you have to watch in that situation is that some
SSRIs (among other kinds of drugs, and grapefruit juice) will inhibit
the metabolism
of tricyclic antidepressants, leading to higher-than-expected blood
levels, with the potential for href="http://www.emedicine.com/ped/topic2714.htm">toxicity.

One relative disadvantage of amitriptyline, as with all tricyclic
antidepressants, is that they can be toxic if the blood level gets much
higher than the therapeutic range.  Therefore, it sometimes is
necessary to check blood levels.   That is expensive, and it
annoys people when you stick needles in them.

Amitriptyline is not a good choice for person prone to overdose, or
persons susceptible to href="http://en.wikipedia.org/wiki/Anticholinergic">anticholinergic
adverse effects (elderly persons, persons with urinary tract or bowel
obstruction, or with narrow-angle glaucoma).  Amitriptyline
has a lot of potential for drug interactions, so it often is not a good
choice for persons taking several different medications.

Comments

  1. #1 Taylor Murphy
    May 31, 2007

    It seems that on your antidepressants page, only two sections come up, namely Selection of Antidepressants, Pt. 4 and Pt. 5. Maybe some of them got lost or mislabeled.

    For those who are looking for more but can’t see them, you can find them by using the search box (top left.)

  2. #2 Joseph j7uy5
    May 31, 2007

    Thanks. It should work now; I had to rebuild the index files.

  3. #3 Greg P
    June 2, 2007

    In retrospect, I think we might say that amitriptyline wasn’t a very good drug for depression, since the benefits were typically less than ideal for the amount of side effects at therapeutic doses.

    I use it a lot for neuropathic pain, in many cases in addition to other things, but it certainly is the cheapest drug out there for that purpose, off-label or on.

    Occasionally I’ll use it in a patient with ALS to help reduce the excessive salivation that some have.

    The curious thing I am seeing lately from insurance companies about off-label drug use is that if a drug is cheap, off-label is OK, and in fact they may require use of the cheap off-label drug before they OK the newer on-label drug. If the off-label drug is expensive, they act as if they don’t allow off-label use of drugs. This has happened to me trying to use some of the new drugs actually FDA-approved for neuropathic pain, and they even push it so far as to make the technical distinction between diabetic neuropathy pain vs. neuropathy pain in a nondiabetic. What a bunch of turds.

  4. #4 Julia
    February 2, 2012

    I was prescribed this for my depression, but the side effects were horrible, not to speak about the withdrawal side effects.

    Glad there are other drugs available now.

  5. #5 afrika mangosu
    February 7, 2012

    I am seeing lately from insurance companies about off-label drug use is that if a drug is cheap, off-label is OK, and in fact they may require use of the cheap off-label drug before