2011 Mao Handbook

The MAO Handbook
Every effort has been made in preparing this book to provide accurate and up-to-date
information that is in accord with accepted standards and practice at the time of pub-
lication. Nevertheless, the author, editors, and publisher can make no warranties that
the information contained herein is totally free from error, not least because clinical
standards are constantly changing through research and regulation. The author, edi-
tors, and publisher therefore disclaim all liability for direct or consequential damages
resulting from the use of material contained in this book. Readers are strongly advised
to pay careful attention to information provided by the manufacturer of any drugs or
equipment that they plan to use.
PUBLISHED BY NEI PRESS, an imprint of NEUROSCIENCE EDUCATION INSTITUTE

Carlsbad, California, United States of America
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Copyright 2011 Neuroscience Education Institute.

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Electronic versions, January 2012
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ii
Table of Contents
CME Information...........................................................................................................................v
Objectives.......................................................................................................................................ix
Chapter 1: Monoamine Oxidase Inhibitors (MAOIs): The Basics..................................1
Chapter 2: Myth #1: The Tyramine Reaction.......................................................................11
Chapter 3: Myths #2 and #3: The Cold Medication/Stimulant Interaction..............23
Chapter 4: Myth #4: The Anesthetic Interaction................................................................31
Chapter 5: Myth #5: The Tricyclic Interaction.....................................................................37
Chapter 6: Myth #6: The Painkiller Interaction...................................................................43
Chapter 7: Myth #7: The Psychotropic Concomitant Medication Interaction........49
Chapter 8: MAOIs: Tips and Pearls..........................................................................................61
Summary.........................................................................................................................................67
Suggested Reading.....................................................................................................................69
CME Posttest and Certificate....................................................................................................71
iii
The MAO Handbook
iv
CME Information
Overview
Despite the fact that MAO inhibitors (MAOIs) can be highly effective therapeutic agents for depression and
some anxiety disorders, they tend to be underutilized in clinical practice. Because these drugs are no longer
emphasized in medical education, there is a great deal of misinformation and mythology about their dietary
and drug interactions. This book is intended to serve as a guide for clinicians who are not particularly familiar
with MAO inhibitors; its aim is to help these clinicians competently integrate these agents into clinical prac-
tice when appropriate.
Target Audience
This activity has been developed for psychiatrists specializing in psychopharmacology. There are no prereq-
uisites. All other health care providers who are interested in psychopharmacology are welcome for advanced
study, especially primary care physicians, nurse practitioners, psychologists, and pharmacists.
Statement of Need
The following unmet needs and professional practice gaps regarding depression were revealed following a
critical analysis of activity feedback, expert faculty assessment, and literature review, as well as through new
medical knowledge:
The timely detection, diagnosis, and treatment of major depression have been shown to increase the
probability of positive clinical outcomes; however, only 60% of those with depression are actually
being treated.
Even when correctly diagnosed and treated, as many as two-thirds of MDD patients will not respond
to the first antidepressant prescribed, a substantial number may be treatment resistant.
To help fill these unmet needs, quality improvement efforts need to provide education regarding under-used
evidence-based treatment strategies for patients with treatment-resistant depression.
Learning Objectives
After completing this educational activity, participants should be better able to:
Identify foods that can or cannot be consumed by patients on different types of MAO inhibitors
Identify medications that can or cannot be taken by patients on different types of MAO inhibitors
Implement safe management strategies when switching between MAO inhibitors and serotonin
reuptake inhibitors
Integrate MAO inhibitors into clinical practice according to best practices standards
Accreditation and Credit Designation Statements

The Neuroscience Education Institute is accredited by the Accreditation Council for Continuing Medical
Education (ACCME) to provide continuing medical education for physicians.
The Neuroscience Education Institute designates this enduring material for a maximum of 3.0 AMA PRA
Category 1 Credits TM. Physicians should claim only the credit commensurate with the extent of their
participation in the activity.
Nurses: for all of your CE requirements for recertification, the ANCC will accept category 1 credits from
organizations accredited by the ACCME.
Physician Assistants: the NCCPA accepts AMA PRA Category 1 Credit from organizations accredited by the AMA/
ACCME.
A certificate of participation for completing this activity will also be available.
v
The MAO Handbook
Please note: the content of this electronic book activity also exists as a print monograph under the same title. If you
received CME credit for the print monograph version, you will not be able to receive credit again for completing this
electronic book version.
Activity Instructions
This CME activity is available in the form of a printed monograph and an electronic book and incorporates
instructional design to enhance your retention of the information and pharmacological concepts that are
being presented. You are advised to read the book in sequence, and then complete the posttest and activity
evaluation. The estimated time for completion of this activity is 3.0 hours.
Instructions for CME Credit

To receive your certificate of CME credit or participation, please complete the posttest and activity evaluation,
available only online, by clicking the link found at the end of this electronic book or at www.neiglobal.
com/CME (under Book). If a passing score of 70% or more is attained (required to receive credit), you can
immediately print your certificate. There is no fee for CME credits for this activity.
NEI Disclosure Policy

It is the policy of the Neuroscience Education Institute to ensure balance, independence, objectivity, and
scientific rigor in all its educational activities. Therefore, all individuals in a position to influence or control
content development are required by NEI to disclose any financial relationships or apparent conflicts of
interest that may have a direct bearing on the subject matter of the activity. Although potential conflicts
of interest are identified and resolved prior to the activity being presented, it remains for the participant
to determine whether outside interests reflect a possible bias in either the exposition or the conclusions
presented.
These materials have been peer-reviewed to ensure the scientific accuracy and medical relevance of
information presented and its independence from commercial bias. The Neuroscience Education Institute
takes responsibility for the content, quality, and scientific integrity of this CME activity.
Individual Disclosure Statements

Authors
Meghan Grady
Director, Content Development, Neuroscience Education Institute, Carlsbad, CA
No other financial relationships to disclose.
Stephen M. Stahl, MD, PhD

Adjunct Professor, Department of Psychiatry, University of California, San Diego School of Medicine
Honorary Visiting Senior Fellow, University of Cambridge, UK
Grant/Research: AstraZeneca, BioMarin, Dainippon Sumitomo, Dey, Forest, Genomind, Lilly, Merck, Pamlab,
Pfizer, PGxHealth/Trovis, Schering-Plough, Sepracor/Sunovion, Servier, Shire, Torrent
Consultant/Advisor: Advent, Alkermes, Arena, AstraZeneca, AVANIR, BioMarin, Biovail, Boehringer
Ingelheim, Bristol-Myers Squibb, CeNeRx, Cypress, Dainippon Sumitomo, Dey, Forest, Genomind, Janssen,
Jazz, Labopharm, Lilly, Lundbeck, Merck, Neuronetics, Novartis, Ono, Orexigen, Otsuka, Pamlab, Pfizer,
PGxHealth/Trovis, Rexahn, Roche, Royalty, Schering-Plough, Servier, Shire, Solvay/Abbott, Sunovion/
Sepracor, Valeant, VIVUS
Speakers Bureau: Dainippon Sumitomo, Forest, Lilly, Merck, Pamlab, Pfizer, Sepracor/Sunovion, Servier,
Wyeth
Peer Reviewer
Steven S. Simring, MD, MPH
Clinical Associate Professor, Department of Psychiatry, Columbia University College of Physicians and Surgeons,
New York State Psychiatric Institute, New York City
vi
CME Information
Design Staff
Nancy Muntner
Director, Medical Illustrations, Neuroscience Education Institute, Carlsbad, CA
Program Development
The following are employed by the Neuroscience Education Institute in Carlsbad, CA, and have no other
financial relationships to disclose.
Rory Daley, MPH, Associate Director, Program Development
Steve Smith, President and COO
Disclosed financial relationships have been reviewed by the Neuroscience Education Institute CME Advisory
Board to resolve any potential conflicts of interest. All faculty and planning committee members have
attested that their financial relationships do not affect their ability to present well-balanced, evidence-based
content for this activity.
Disclosure of Off-Label Use

This educational activity may include discussion of products or devices that are not currently labeled for such
use by the FDA. Please consult the product prescribing information for full disclosure of labeled uses.
Disclaimer
The information presented in this educational activity is not meant to define a standard of care, nor is it
intended to dictate an exclusive course of patient management. Any procedures, medications, or other
courses of diagnosis or treatment discussed or suggested in this educational activity should not be used by
clinicians without full evaluation of their patients conditions and possible contraindications or dangers in
use, review of any applicable manufacturers product information, and comparison with recommendations of
other authorities. Primary references and full prescribing information should be consulted.
Participants have an implied responsibility to use the newly acquired information from this activity to
enhance patient outcomes and their own professional development. The participant should use his/her
clinical judgment, knowledge, experience, and diagnostic decision-making before applying any information,
whether provided here or by others, for any professional use
Sponsorship Information
This activity is sponsored by the Neuroscience Education Institute.
Support
This activity is supported by an educational grant from Dey Pharma, L.P.
Date of Release/Expiration
Print Monograph Released: December 15, 2011
Electronic Books Released: January, 2012
CME Credit Expires: December 14, 2014
vii
The MAO Handbook
viii
Objectives
Identify foods that can or cannot be consumed by patients on different types

of MAO inhibitors
Identify medications that can or cannot be taken by patients on different
types of MAO inhibitors
Implement safe management strategies when switching between MAO
inhibitors and serotonin reuptake inhibitors
Integrate MAO inhibitors into clinical practice according to best practices
standards
ix
The MAO Handbook
x
Chapter 1
Monoamine Oxidase Inhibitors (MAOIs):
The Basics
1
The MAO Handbook
Monoamine Oxidase (MAO)
FIGURE 1.1. The first clinically effective antidepressants discovered were

inhibitors of the enzyme monoamine oxidase (MAO). Today, there are several agents
with variations of this mechanism of action. Despite the fact that MAO inhibitors
(MAOIs) can be highly effective therapeutic agents for depression and some
anxiety disorders, they tend to be underutilized in clinical practice. There are many
reasons for this, including the fact that there are many other treatment options,
which prevent clinicians from becoming familiar with MAO inhibitors. Because
these drugs are no longer emphasized in medical education, there is a great deal
of misinformation and mythology about their dietary and drug interactions. This
book is intended to serve as a guide for clinicians who are not particularly familiar
with MAO inhibitors; its aim is to help these clinicians competently integrate these
agents into clinical practice when appropriate.
2
Chapter 1: Monoamine Oxidase Inhibitors (MAOIs) - The Basics
MAO Subtypes
TABLE 1.1.
MAO-A MAO-B
Substrates Serotonin (5HT)
Norepinephrine
Dopamine Dopamine
Tyramine Tyramine
Phenylethylamine
Tissue distribution Brain, gut, liver, placenta, Brain, platelets,
skin lymphocytes
TABLE 1.1. MAO is an enzyme that metabolizes monoamines as well as trace

amines. It exists in two subtypes: A and B. The A form preferentially metabolizes
the monoamines most closely linked to depression (i.e., serotonin and
norepinephrine), whereas the B form preferentially metabolizes trace amines such
as phenylethylamine. Both MAO-A and MAO-B metabolize dopamine and tyramine,
and both are present in the brain. Noradrenergic and dopaminergic neurons are
thought to contain both MAO-A and MAO-B, perhaps with MAO-A activity being
predominant, whereas serotonergic neurons are thought to contain only MAO-B.
With the exception of platelets and lymphocytes, which have MAO-B, MAO-A is the
major form of this enzyme outside of the brain.
3
The MAO Handbook
MAO-A Inhibition:
Antidepressant Action
4
FIGURE 1.2. An MAO inhibitor must inhibit MAO-A in the brain in order
for antidepressant efficacy to occur. This is not surprising given that MAO-A
preferentially metabolizes serotonin and norepinephrine, the two monoamines
most strongly implicated in depression and the mechanisms of antidepressants
(left, top two frames). MAO-A (along with MAO-B) also metabolizes dopamine (left,
bottom frame).
This means that MAO-A inhibition increases serotonin, norepinephrine, and

dopamine (right frames), but that the increase in dopamine is not as great as that
of serotonin and norepinephrine, since MAO-B can still metabolize dopamine
(right, bottom frame).
5
The MAO Handbook
MAO-B Inhibition:
No Antidepressant Action
6
FIGURE 1.3. The inhibition of MAO-B is not effective as an antidepressant.

This is because MAO-B metabolizes serotonin and norepinephrine only at high
concentrations (left, top two frames). Since the role of MAO-B in destroying
serotonin and norepinephrine is small, the inhibition of MAO-B is not likely to be
relevant to the concentrations of these neurotransmitters (right, top two frames).
The selective inhibition of MAO-B also has somewhat limited effects on dopamine
concentrations because MAO-A continues to destroy dopamine. However,
the inhibition of MAO-B does increase dopamine to some extent; this can be
therapeutic in other disease states, such as enhancing the efficacy of levodopa in
Parkinsons disease.
7
The MAO Handbook
MAO-A and MAO-B Inhibition:

Robust Antidepressant Action
8
FIGURE 1.4. The combined inhibition of MAO-A and MAO-B may have robust
antidepressant actions owing to increases in not only serotonin and norepinephrine,
but also dopamine. The inhibition of both MAO-A, which metabolizes all three
monoamines, and MAO-B, which metabolizes primarily dopamine (left frames),
leads to greater increases in each of these neurotransmitters than the inhibition of
either enzyme alone (right frames).
9
The MAO Handbook
Monoamine Oxidase Inhibitors
TABLE 1.2.
Name Inhibition of Inhibition of Amphetamine
MAO-A MAO-B Properties
phenelzine + +
tranylcypromine + + +
isocarboxazid + +
amphetamines
+ + +
(high-dose)
selegiline
(transdermal)
brain + + +
gut +/- + +
selegiline
- + +
(oral low-dose)
rasagiline
- + -
(Europe, Israel)
moclobemide
+ - -
(not in U.S.)
CX 157 + - -
TABLE 1.2. Currently available MAO inhibitors include phenelzine,

tranylcypromine, and isocarboxazid, which are irreversible inhibitors of both
MAO-A and MAO-B; amphetamine, which is a weak inhibitor of MAO-A and MAO-B;
transdermal selegiline, which inhibits both MAO-A and MAO-B in the brain but
predominantly MAO-B in the gut; oral low-dose selegiline and rasagiline, which are
selective for MAO-B; and moclobemide, which is a reversible inhibitor of MAO-A
that is available outside of the United States.
10
Chapter 2
Myth #1:
The Tyramine Reaction
11
The MAO Handbook
The Myth
You cant eat cheese, drink wine or beer, or eat
lots of foods that contain tyramine, or else you
will develop hypertensive crisis...
so if you go to pizza parties or wine and

cheese receptions, eat in restaurants, or follow a
normal diet, you cant take an MAOI.
12
Chapter 2: Myth #1 - The Tyramine Reaction
The Truth
There are a few things to avoid (which are easy
to remember), but in practice, diet is not really a
problem
unless you plan to eat more than 25 pieces of

pizza or drink more than 25 cans of beer or 25
glasses of wine.
13
The MAO Handbook
The Pharmacology
You should be cautious when combining
an MAOI with anything that boosts
norepinephrine because this can
raise blood pressure.
14
The Pharmacology
FIGURE 2.1. One of the biggest barriers to using MAO inhibitors has traditionally
been the risk that a patient taking one of these drugs may develop a hypertensive
reaction after ingesting tyramine in the diet.
How might the combination of tyramine in the diet plus MAO inhibition lead to a
dangerous elevation in blood pressure? Tyramine works to elevate blood pressure
because it is a potent releaser of norepinephrine. However, MAO-A normally acts to
destroy norepinephrine to keep it in balance. Since accumulated norepinephrine
can cause vasoconstriction and elevated blood pressure via increased binding at
alpha-1 and other adrenergic receptors, its normal destruction by MAO-A helps
prevent these negative effects.
15
The MAO Handbook
The Pharmacology (cont.)
FIGURE 2.2. Tyramine is an amine that causes norepinephrine release (1). When
foods high in tyramine content are ingested, MAO-A in the intestinal wall destroys
tyramine before it is absorbed; MAO-A in the liver destroys any tyramine that gets
absorbed; and if any tyramine reaches the noradrenergic sympathetic neuron,
MAO-A readily destroys the excess norepinephrine released by tyramine (2), and
no harm is done (i.e., no vasoconstriction or elevation in blood pressure).
The body thus has a huge capacity for processing tyramine, and the average person
is able to handle around 400 mg of ingested tyramine before their blood pressure
becomes elevated. A high-tyramine diet, by contrast, includes only around 40 mg
of tyramine.
16
The Pharmacology (cont.)
FIGURE 2.3. When MAO-A is inhibited, the bodys capacity to handle dietary
tyramine is greatly reduced, and a high-tyramine meal is sufficient to raise blood
pressure when a substantial amount of MAO-A is irreversibly inhibited. That is,
tyramine increases the release of norepinephrine (1). However, MAO-A is also
inhibited by an irreversible MAO-A inhibitor (2). This results in MAO-A stopping
its destruction of norepinephrine (2). When MAO-A inhibition takes place in the
presence of tyramine, the combination can lead to a very large accumulation of
norepinephrine (3). Such an accumulation can lead to excessive stimulation of
postsynaptic adrenergic receptors (3) and therefore dangerous vasoconstriction
and elevation of blood pressure.
17
The MAO Handbook
Hypertensive Crisis
TABLE 2.1.
Defined by diastolic blood pressure >120 mmHg
Potentially fatal reaction characterized by:
Occipital headache that may radiate frontally
Palpitation
Neck stiffness or soreness
Nausea
Vomiting
Sweating (sometimes with fever)
Dilated pupils, photophobia
Tachycardia or bradycardia, which can be associated with
constricting chest pain
TABLE 2.1. It may take as little as 10 mg of dietary tyramine to increase blood

pressure when MAO-A is essentially knocked out by high doses of an MAO inhibitor.
Some blood pressure elevations can be very large, sudden, and dramatic, causing
a condition known as hypertensive crisis, which can rarely cause intracerebral
hemorrhage or even death.
18
The Owners Manual:

Recommended Dietary Restrictions for MAOIs*
TABLE 2.2.
Foods to avoid Foods allowed
Dried, aged, smoked, fermented, spoiled, Fresh or processed meat, poultry, and
or improperly stored meat, poultry, and fish; properly stored pickled or smoked
fish fish
Broad bean pods All other vegetables
Aged cheeses Processed cheese slices, cottage cheese,
ricotta cheese, yogurt, cream cheese
Tap and unpasteurized beer Canned or bottled beer and alcohol
Marmite Brewers and bakers yeast
Sauerkraut, kimchee
Soy products/tofu Peanuts
Banana peel Bananas, avocados, raspberries
Tyramine-containing nutritional
supplement
TABLE 2.2. Because of the potential danger of a hypertensive crisis from

a tyramine reaction in patients taking irreversible MAO inhibitors, a certain
mythology has grown up around how much tyramine is in various foods and which
dietary restrictions are necessary. Since the tyramine reaction is sometimes called a
cheese reaction, there is a myth that all cheese must be restricted. That is true only
for aged cheeses, but not for most processed cheese and for most cheese utilized
in most commercial chain pizzas. Thus, it is not true that patients on MAO inhibitors
must avoid the ingestion of any cheese. It is also not true that such patients must
avoid all beer and wine. Canned and bottled beers are low in tyramine; generally,
only tap and unpasteurized beers must be avoided. Many wines are actually quite
low in tyramine. Of course, prescribers should counsel patients taking the classic
MAO inhibitors about diet and keep current with the tyramine content of the foods
their patients wish to eat.
*Not necessary for 6 mg transdermal or low-dose oral selegiline
19
The MAO Handbook
Reversible Monoamine Oxidase A

Inhibitors (RIMAs)
FIGURE 2.4. How can one inhibit MAO-A to achieve antidepressant actions but
not inhibit MAO-A to avoid tyramine reactions? One method is through reversible
inhibition of MAO-A. Irreversible inhibition of MAO-A, as with the older MAO
inhibitors, prevents the enzyme from ever functioning again; enzyme activity
returns only after a new enzyme is synthesized. Reversible inhibitors of MAO-A
(RIMAs), on the other hand, can be removed from the enzyme by competitors. Thus,
when tyramine increases norepinephrine release (1), it increases the competition
for MAO-A. RIMAs can then be displaced (2), allowing for normal destruction of the
extra norepinephrine (3) and reducing the risk of a tyramine reaction.
20
Transdermal Delivery of Selective

MAO-B Inhibitors
FIGURE 2.5. Another method of reducing the risk of tyramine reactions while
continuing to exert antidepressant effects is the use of a transdermal delivery
system for selegiline. Selegiline is a selective MAO-B inhibitor at low doses, and
it must be administered in high doses in order to inhibit MAO-A. Delivering
selegiline through a transdermal patch enables the inhibition of both enzymes in
the brain while bypassing the inhibition of MAO-A in the gut. That is, transdermal
delivery is like an intravenous infusion without a needle, delivering a drug directly
into systemic circulation, hitting the brain in high doses, and avoiding a first pass
through the liver. By the time the drug recirculates to the intestine and the liver, it
has much decreased levels, and it significantly inhibits only MAO-B in these tissues.
21
The MAO Handbook
How Much Tyramine Is Dangerous

With MAO Inhibitors?
FIGURE 2.6. A meal that contains 40 mg of tyramine is considered high in this

substance; however, in normal individuals (i.e., those not taking an MAO-A inhibitor),
it takes as much as 400 mg of tyramine to elevate blood pressure (far right column).
Patients taking low-dose oral selegiline, which inhibits only MAO-B, may ingest
as much tyramine as those not taking an MAO inhibitor; however, they will not
experience any antidepressant effect (fourth column). In contrast, patients taking
a nonselective irreversible MAO inhibitor, such as tranylcypromine or phenelzine,
may be able to ingest as little as 10 mg of tyramine before experiencing a tyramine
reaction (first column). These patients experience antidepressant effects but are at
high risk for a tyramine reaction. Transdermal selegiline, on the other hand, inhibits
MAO-A and MAO-B in the brain but mosty MAO-B in the gut; this means that it
achieves antidepressant efficacy but is less likely to cause a tyramine reaction.
Patients taking transdermal selegiline may be able to ingest a high-tyramine meal
of 40 mg or more with safety. This has been proven for the 6 mg dose but there is
insufficient data to confirm this for the 9 and 12 mg doses.
22
Chapter 3
Myths #2 and #3:
The Cold Medication/Stimulant
Interaction
23
The MAO Handbook
The Myths
You cant take cold medications, such as
decongestants, antihistamines, or cough
medicines, with MAOIs, so patients who get
colds cannot take MAOIs.
You cant take stimulants with MAOIs, so

patients who need stimulants cannot take
MAOIs.
24
Chapter 3: Myths #2 and #3 - The Cold Medication/Stimulant Interaction
The Truth
Sympathomimetic decongestants and
stimulants should be used with caution while
monitoring blood pressure in patients for which
the benefits are greater than the risks and
should be avoided only in high-risk/low-benefit
populations.
25
The MAO Handbook
The Pharmacology
norepinephrine because this can raise blood
pressure.
You should completely avoid combining an

MAOI with anything that blocks serotonin
reuptake because this can cause a dangerous or
fatal serotonin syndrome/toxicity.
26
The Pharmacology
FIGURE 3.1. Decongestants that stimulate postsynaptic alpha-1 receptors, such as

phenylephrine, may interact with MAO inhibitors to increase the risk of hypertension.
Decongestants work by constricting nasal blood vessels, but they do not typically
elevate blood pressure at therapeutic doses. However, the direct alpha-1 stimulation
of a decongestant combined with the noradrenergic action of an MAO inhibitor may
be sufficient to cause hypertension or even hypertensive crisis.
27
The MAO Handbook
The Owners Manual:

Drugs That Boost Norepinephrine and Thus
Should Be Used With Caution With MAO Inhibitors
TABLE 3.1.
Decongestants Stimulants Antidepressants Other
With NRIs
Phenylephrine Amphetamine Most TCAs Phentermine
Pseudoephedrine Methylphenidate NRIs Local anesthetics
containing
vasoconstrictors
Modafinil SNRIs Tramadol,
tapentadol
Armodafinil NDRIs Cocaine,
methamphetamine
TABLE 3.1. For patients with colds who are on MAO inhibitors, it is probably
best to use antihistamines, which are safe with the exception of those that are also
serotonin reuptake inhibitors (e.g., brompheniramine and chlorpheniramine). Cough
medicines with expectorants or codeine are safe, but avoid dextromethorphan, a
weak serotonin reuptake inhibitor.
Stimulants are useful as bridging medications when starting or stopping MAOIs

and as augmenting medications to boost partial response to MAOIs. They should
not be used in patients who are known cocaine/methamphetamine/stimulant
abusers. Although formally contraindicated, stimulants can be given by experts
with caution and appropriate monitoring, either as augmenting agents or bridging
medications.
28
Drug Interaction Data:

Transdermal Selegiline and Sympathomimetics
Table 3.2. Mean systolic and diastolic blood pressure (SBP and DBP) and heart
rate (HR) before and during multiple-dose treatment with a sympathomimetic
[pseudoephedrine (PSE) or phenylpropanolamine (PPA)] and/or transdermal
selegiline (TS) 6 mg/24 hr
Baseline End of PSE Treatment
Parameter Untreated TS PSE TS + PSE
Control
SBP (mm Hg) 118.4 109.1 122.9 122.2
DBP (mm Hg) 71.0 63.2 68.9 67.9
HR (bpm) 62.7 59.4 73.5 75.5
Baseline End of PPA Treatment
Parameter Untreated TS PPA TS + PPA
Control
SBP (mm Hg) 120.2 123.5 121.2 125.1
DBP (mm Hg) 72.3 71.2 71.9 74.0
HR (bpm) 64.7 64.3 62.2 64.1
TABLE 3.2. Small, open-label studies have been conducted to investigate

potential drug-drug interactions between pseudoephedrine and transdermal
selegiline (Azzaro et al., 2007). Change in heart rate and blood pressure was evaluated
in a sample of 25 healthy controls during administration of pseudoephedrine (or
phenylpropanolamine) alone, transdermal selegline alone, or the combination. No
significant differences were found. Nonetheless, the combination of transdermal
selegiline with sympathomimetics is still formally contraindicated.
29
The MAO Handbook
30
Chapter 4
Myth #4:
The Anesthetic Interaction
31
The MAO Handbook
The Myth
You cant have a local or a general anesthetic
when on an MAOI, so patients who need dental
work, stitches, or surgery cannot take an MAOI.
32
Chapter 4: Myth #4 - The Anesthetic Interaction
The Truth
Be careful using local anesthetics that contain
epinephrine and also be careful using general
anesthesia, as both can cause blood pressure
changes.
33
The MAO Handbook
The Pharmacology
Pressor agents inadvertently injected
intravenously can raise blood pressure;
inhalation anesthetics can cause
blood pressure changes.
34
Chapter 4: Myth #4 - The Anesthetic Interaction
The Owners Manual:

Use of Anesthetics
Table 4.1.
Local anesthetic Elective surgery Urgent or elective
surgery when patient
is still taking an MAO
inhibitor
Choose an agent Wash out the MAO Cautiously use a
that does not contain inhibitor 10 days prior to benzodiazepine,
vasoconstrictors surgery mivacurium,
rapacuronium, morphine,
or codeine
TABLE 4.1. For a patient taking an MAO inhibitor who needs to have a local
anesthetic, choose an agent that does not contain vasoconstrictors. For elective
surgery, one should wash out the MAO inhibitor 10 days prior to the surgery. For
urgent surgery or elective surgery when the patient is still taking an MAO inhibitor,
one can cautiously use a benzodiazepine, mivacurium, rapacuronium, morphine,
or codeine.
35
The MAO Handbook
36
Chapter 5
Myth #5:
The Tricyclic Interaction
37
The MAO Handbook
The Myth
Tricyclic antidepressants are so dangerous that
patients on MAO inhibitors cannot take them
or anything that resembles them, including
carbamazepine and cyclobenzaprine.
38
Chapter 5: Myth #5 - The Tricyclic Interaction
The Truth
Other than clomipramine, tricyclic
antidepressants and related agents can be used
with caution in patients taking MAO inhibitors.
39
The MAO Handbook
The Pharmacology

40
Chapter 5: Myth #5 - The Tricyclic Interaction
The Owners Manual:

Using Tricyclic Antidepressants With
MAO Inhibitors
Table 5.1.
Contraindicated Use with caution
clomipramine other tricyclic antidepressants
cyclobenzaprine
carbamazepine
oxcarbazepine
TABLE 5.1. The only tricyclic antidepressant to be strictly avoided in combination

with an MAO inhibitor is clomipramine. Other tricyclic antidepressants can be used
with caution for severely treatment-resistant patients. If this option is selected,
one should start the MAO inhibitor at the same time as the tricyclic antidepressant
(both at low doses) after an appropriate drug washout; then, one should alternately
increase the doses of these agents every few days to a week as tolerated. The MAOI
should not be started first.
Cyclobenzaprine, carbamazepine, and oxcarbazepine can be used with caution

because they do not block serotonin or norepinephrine reuptake.
41
The MAO Handbook
42
Chapter 6
Myth #6:
The Painkiller Interaction
43
The MAO Handbook
The Myth
You cant take painkillers with MAOIs because
they will kill you, so patients who have sprained
ankles, sore muscles, dental extractions, or
surgeries cannot take MAOIs, as they must
avoid all opiate and non-opiate painkillers.
44
Chapter 6: Myth #6 - The Painkiller Interaction
The Truth
There are a few things to avoid (which are easy
to remember), and in practice, this is not really
a problem.
45
The MAO Handbook
The Pharmacology
There is no interaction of MAOIs with opiate
mechanisms; however, meperidine is a potent
serotonin reuptake inhibitor and should be
avoided.
Methadone and tramadol are weak serotonin

reuptake inhibitors and should be avoided.
Tapentadol is a norepinephrine reuptake

inhibitor and should be avoided.
46
Chapter 6: Myth #6 - The Painkiller Interaction
The Owners Manual:

Using Painkillers With MAO Inhibitors
Table 6.1.
Use With MAOIs Should Use With MAOIs Not Use With MAOIs Strictly
Be Cautious Recommended But May Prohibited
Sometimes Be Done By
Experts
acetaminophen hydromorphone fentanyl
aspirin morphine meperidine
buprenorphine oxycodone methadone
butophanol oxymorphone tapentadol
codeine tramadol
hydrocodone
nalbuphine
NSAIDs
pentazocine
TABLE 6.1. There is no interaction between MAOIs and opioid mechanisms;

instead, the reason why some opioids must be avoided is that certain agents
meperidine, methadone, and tramadolhave serotonin reuptake inhibition, while
tapentadol has norepinephrine reuptake inhibition.
47
The MAO Handbook
48
Chapter 7
Myth #7:
The Psychotropic Concomitant
Medication Interaction
49
The MAO Handbook
The Myth
Since you cant take any medications that block
serotonin reuptake while taking an MAOI, you
cant take any psychotropic medications. Since
all patients who are candidates for an MAOI
need concomitant medications, no one can
take an MAOI.
Besides, you cannot get there from here

because in order to start an MAOI, you have to
disrupt everything, stopping all other meds for
2 weeks after taper. And if you have to stop an
MAOI to go back to a psychotropic medication,
you have to go without all meds for another 2
weeks. This is an unacceptable risk and a hassle.
50
Chapter 7: Myth #7 - The Psychotropic Concomitant Medication Interaction
The Truth
You must completely avoid only agents
that block serotonin reuptake. There are
many options for not only bridging between
serotonin reuptake inhibitors and MAOIs, but
also augmenting MAOIs.
51
The MAO Handbook
The Pharmacology

52
The Pharmacology
FIGURE 7.1. This figure illustrates the mechanism by which serotonin reuptake
inhibition combined with MAO inhibition can lead to serotonin toxicity. The
inhibition of the serotonin transporter (SERT) leads to the increased synaptic
availability of serotonin (1). Similarly, the inhibition of MAO leads to increased
serotonin levels (2). In combination, these two mechanisms can cause excessive
stimulation of postsynaptic serotonin receptors, the most important of which is
perhaps the 5HT2A receptor in the hypothalamus.
53
The MAO Handbook
Serotonin Toxicity:
Potential Clinical Features
Table 7.1.
Neuromuscular Autonomic Altered mental status
hyperactivity hyperactivity
Akathisia Diaphoresis Agitation
Tremor Fever Excitement
Clonus Tachycardia Confusion
Myoclonus Tachypnea
Hyperreflexia
Rigidity
Nystagmus
TABLE 7.1. Any agent with serotonin reuptake blockade has the potential
to cause a fatal serotonin syndrome or serotonin toxicity. The general clinical
features of serotonin toxicity can range from migraines, myoclonus, agitation,
and confusion on the mild end of the spectrum, to hyperthermia, seizures, coma,
cardiovascular collapse, permanent hyperthermic brain damage, and even death
at the severe end of the spectrum. For this reason, it is important to closely monitor
all concomitant medications in patients on MAO inhibitors, even in patients taking
RIMAs or transdermal selegiline, for which these drug interactions also apply.
54
Serotonin Toxicity:
Sternbach Criteria
Table 7.2.
Recent addition or increase in a known serotonergic agent
Absence of other possible etiologies (infection, substance abuse, withdrawal, etc.)
No recent addition or increase of a neuroleptic agent
At least three of the following:
Agitation
Myoclonus
Hyperreflexia
Diaphoresis
Shivering
Tremor
Diarrhea
Ataxia/incoordination
Fever
TABLE 7.2. Early diagnostic criteria for serotonin toxicity (syndrome) were
developed by Sternbach based on examination of published case reports and are
listed above. However, these criteria can lack both sensitivity and specificity.
55
The MAO Handbook
Serotonin Toxicity:
Hunter Criteria
Table 7.3.
Clinical Decision Rules:
Features In the presence of a serotonergic agent
Clonus IF (spontaneous clonus=yes) THEN serotonin toxicity=YES
Agitation ELSE IF (inducible clonus=yes) AND [(agitation=yes) OR
(diaphoresis=yes) THEN serotonin toxicity=YES
Diaphoresis ELSE IF (ocular clonus=yes) AND [(agitation=yes) OR
(diaphoresis=yes) THEN serotonin toxicity=YES
Tremor ELSE IF (tremor=yes) AND (hyperreflexia=yes) THEN serotonin
toxicity=YES
Hyperreflexia ELSE IF (hypertonic=yes) AND (temperature>38C) AND
[(ocular clonus=yes) OR (inducible clonus=yes)] THEN serotonin
toxicity=YES
Hypertonicity ELSE serotonin toxicity=NO
Hyperpyrexia
TABLE 7.3. The apparent limitations of the Sternbach criteria for serotonin
toxicity prompted another group to develop a set of diagnostic criteria. These
criteriacalled the Hunter Serotonin Toxicity Criteriaare based on retrospective
analysis of more than 2200 patients who experienced overdose from a serotonergic
drug. It was determined that only five of the clinical features associated with
serotonin toxicity were needed to make an accurate diagnosis: clonus, agitation,
diaphoresis, tremor, and hyperreflexia. In addition, hypertonicity and hyperpyrexia
were present in all life-threatening cases of serotonin toxicity. They also developed
decision rules for diagnosis, based on the presence or absence of the seven clinical
features.
56
The Owners Manual:

Drugs to Avoid Due to Risk of Serotonin
Syndrome/Toxicity
TABLE 7.4.
Antidepressants Drugs of Abuse Opioids Other
SSRIs MDMA (ecstasy) meperidine non-subcutaneous

triptans
SNRIs cocaine tramadol chlorpheniramine
clomipramine meth- methadone brompheniramine
amphetamine
St. Johns wort High-dose dextro-
or injected methorphan
amphetamine
TABLE 7.4. One can essentially never combine agents that have potent
serotonin reuptake inhibition with agents given in doses that cause substantial
MAO inhibition. This includes any selective serotonin reuptake inhibitor (SSRI);
any serotonin-norepinephrine reuptake inhibitor (SNRI), including the appetite
suppressant sibutramine; and the tricyclic antidepressant clomipramine.
Opioids that block serotonin reuptake, especially meperidine but also tramadol,
methadone, and dextromethorphan, must also be avoided when an MAO inhibitor
is given. Several drugs of abuse (listed above) also block serotonin reuptake; thus,
diligent questioning about drug use is necessary when considering prescribing an
MAO inhibitor.
Although it is commonly believed that serotonin 1A partial agonism could

contribute to serotonin syndrome, this mechanism is not actually a contraindication
for combination with MAO inhibition.
57
The MAO Handbook
The Owners Manual:

Switching From a Serotonergic Drug to an MAOI
FIGURE 7.2. Because of the risk of serotonin toxicity, complete washout of a

serotonergic drug is necessary before starting an MAO inhibitor. One must wait
at least 5 half-lives after discontinuing the serotonergic drug before starting the
MAO inhibitor. For most drugs, this means waiting 57 days; a notable exception is
fluoxetine, for which one must wait 5 weeks due to its long half-life.
58
The Owners Manual:

Switching From an MAOI to a Serotonergic Drug
FIGURE 7.3. If one is switching from an MAO inhibitor to a serotonin reuptake

inhibitor, one must wait at least 14 days following the discontinuation of the MAO
inhibitor before starting the serotonergic drug.
59
The MAO Handbook
The Owners Manual:

How to Bridge
Table 7.4.
Use these drugs while waiting to start an MAOI or when discontinuing an MAOI
benzodiazepines
Z drug hypnotics
trazodone
lamotrigine
valproate
gabapentin, pregabalin, topiramate, carbamazepine, oxcarbazepine
stimulants
atypical antipsychotics
TABLE 7.4. Because there is a required gap in antidepressant treatment when

switching to or from an MAO inhibitor, clinicians may be concerned about
managing symptoms during that time period. There are many medication options,
depending on the individual patients situation. These include benzodiazepines,
Z drug sedative hypnotics, trazodone, lamotrigine, valproate, several other
anticonvulsants, stimulants, and atypical antipsychotics. Specifically, although
trazodone does have serotonin reuptake inhibition at antidepressant doses (i.e.,
150 mg or higher), this property is not clinically relevant at the low doses used for
insomnia while bridging an MAO inhibitor. The atypical antipsychotic ziprasidone
also has serotonin reuptake inhibition, but this is not likely to be potent enough at
therapeutic doses to be a problem.
60
Chapter 8
MAOIs: Tips and Pearls
61
The MAO Handbook
Phenelzine:
Tips and Pearls
Therapeutics Dosing Tips
Mechanism: Formulations:
Irreversible, nonselective MAO inhibitor Tablets: 15 mg
Approved for: Dosage Range:
Depressed patients characterized as 4575 mg/day
atypical, nonendogenous, or neurotic Tips:
Once dosing is stabilized, some patients
Special Populations may tolerate once- or twice-daily dosing
Not recommended for use under rather than 3-times-a-day dosing;
age 16 orthostatic hypotension, especially at high
doses, may require splitting into 4 daily
doses; patients receiving high doses may
Pregnancy risk category C (some need to be evaluated periodically for effects
animal studies show adverse on the liver; little evidence to support
effects; no controlled studies in efficacy below 45 mg/day
humans)
Contraindicated in patients Side Effects and Safety
with congestive heart failure or
hypertension; any other cardiac
impairment may require lower
than usual adult dose; patients
with angina pectoris or coronary
artery disease should limit their
exertion
May require lower dose in patients Hypertensive crisis (especially
with renal impairment; use with when MAOIs are combined with
caution, as drug may accumulate certain tyramine-containing foods
in plasma or prohibited drugs); induction of
mania; rare activation of suicidal
Contraindicated ideation; seizures; hepatotoxicity
FIGURE 8.1. Dosing and safety information for phenelzine.
62
Chapter 8: MAOIs - Tips and Pearls
Tranylcypromine:
Tips and Pearls
Major depressive episode without 30 mg/day in divided doses
melancholia Tips:
Orthostatic hypotension, especially at high
Special Populations doses, may require splitting into 34 daily
Not recommended for use under doses; patients receiving high doses may
age 18 need to be evaluated periodically for effects
on the liver
Pregnancy risk category C (some
animal studies show adverse Side Effects and Safety
effects; no controlled studies in
humans)
Contraindicated in patients with
any cardiac impairment
May require lower dose in patients

with renal impairment; use with Hypertensive crisis (especially
caution, as drug may accumulate when MAOIs are combined with
in plasma certain tyramine-containing foods
Should not be used in patients or prohibited drugs); induction of
with history of hepatic impairment mania; rare activation of suicidal
or in patients with abnormal liver ideation; seizures; hepatotoxicity
function tests
FIGURE 8.2. Dosing and safety information for tranylcypromine.
63
The MAO Handbook
Isocarboxazid:
Tips and Pearls
Depression 4060 mg/day
Tips:
Special Populations Orthostatic hypotension, especially at high
Not recommended for use under doses, may require splitting into 4 daily
age 16 doses; patients receiving high doses may
need to be evaluated periodically for effects
on the liver; little evidence to support
Pregnancy risk category C (some efficacy below 30 mg/day
animal studies show adverse
effects; no controlled studies in
humans) Side Effects and Safety
Contraindicated in patients
with congestive heart failure or
hypertension; any other cardiac
impairment may require lower
than usual adult dose; patients
with angina pectoris or coronary
artery disease should limit their
exertion Hypertensive crisis (especially
when MAOIs are combined with
May require lower dose in patients certain tyramine-containing foods
with renal impairment; use with or prohibited drugs); induction of
caution, as drug may accumulate mania; rare activation of suicidal
in plasma ideation; seizures; hepatotoxicity
Contraindicated
FIGURE 8.3. Dosing and safety information for isocarboxazid.
64
Chapter 8: MAOIs - Tips and Pearls
Selegiline (Transdermal):
Tips and Pearls
MAO-A and MAO-B inhibitor in the brain Transdermal patch: 20 mg/20 cm2
and relatively selective MAO-B inhibitor in (6 mg/24 h), 30 mg/30 cm2 (9 mg/24 h),
the gut 40 mg/40 cm2 (12 mg/24 h)
Major depressive disorder 6 mg/24 h12 mg/24 h
Tips:
Special Populations Transdermal patch contains 1 mg of selegiline
Not recommended for use under per 1 cm2 and delivers approximately 0.3 mg
age 18 of selegiline per cm2 over 24 hours; at 6 mg/24
hours (transdermal), dietary adjustments are
not generally required; dietary modifications
Pregnancy risk category C (some to restrict tyramine intake from foods are
animal studies show adverse recommended for doses above 6 mg/24
effects; no controlled studies in hours (transdermal); because of residual drug
humans) in the patch after 24 hours of administration,
May require lower than usual discard used patches in a manner that
adult dose; observe closely for prevents accidental application or ingestion
orthostatic hypotension by children, pets, or others
No dose adjustment necessary
for transdermal administration in Side Effects and Safety
patients with mild to moderate
renal impairment
No dose adjustment necessary
for transdermal administration in
patients with mild to moderate
hepatic impairment
Hypertensive crisis was not

observed with transdermal patch
in clinical trials; theoretically, at
high doses, can cause induction of
mania, seizures; rare activation of
suicidal ideation
FIGURE 8.4. Dosing and safety information for selegiline.

65
The MAO Handbook
Moclobemide:
Tips and Pearls
Reversible, selective inhibitor of MAO-A Tablets: 100 mg scored, 150 mg scored
Not approved in United States 300600 mg/day
Tips:
Special Populations At higher doses, moclobemide also
Not recommended for use under inhibits MAO-B and thereby loses its
age 18 selectivity for MAO-A, with uncertain
clinical consequences; taking moclobemide
after meals may minimize the chances of
Not generally recommended for interactions with tyramine; may be less toxic
use during pregnancy, especially in overdose than tricyclic antidepressants
during first trimester and older MAO inhibitors; clinical duration
Cardiac impairment may require of action may be longer than biological half-
lower than usual adult dose; life and may allow for twice-daily dosing in
patients with angina pectoris or some patients or even once-daily dosing at
coronary artery disease should low doses
limit their exertion
Use with caution in patients with Side Effects and Safety
renal impairment
Plasma concentrations are

increased in patients with hepatic
impairment; may require one-half
to one-third of usual adult dose
Hypertensive crisis (especially

when MAOIs are combined with
certain tyramine-containing foods
or prohibited drugs); induction of
mania; rare activation of suicidal
ideation; seizures
FIGURE 8.5. Dosing and safety information for moclobemide.
66
Summary
yy MAO inhibitors still play a role in modern psychopharmacology

yy Distinct and understandable pharmacological mechanisms account for
MAOIs and their:
Therapeutic actions
Serotonin syndrome/toxicity
Sympathomimetic drug interactions
Dietary tyramine interactions
yy Dispelling the myths about these older agents and learning the truthas
well as the pharmacology behind itcan allow clinicians to confidently
integrate these agents into clinical practice for patients who do not respond
to first-line treatment
67
The MAO Handbook
68
Suggested Reading
Azzaro AJ, VanDenBerg CM, Ziemniak J, Kemper EM, Blob LF, Campbell BJ. Evaluation of the
potential for pharmacodynamic and pharmacokinetic drug interactions between selegiline
transdermal system and two sympathomimetic agents (pseudoephedrine and phenylpro-
panolamine) in healthy volunteers. J Clin Pharmacol 2007;47(8):978-90.

Bortolato M, Chen K, Shih JC. Monoamine oxidase inactivation: from pathophysiology to
therapeutics. Adv Drug Deliv Rev 2008;60:1527-33.

Gillman PK. Advances pertaining to the pharmacology and interactions of irreversible
nonselective monoamine oxidase inhibitors. J Clin Psychopharmacol 2011;31:66-74.
Stahl SM. Stahls essential psychopharmacology. 3rd ed. New York, NY: Cambridge Univer-
sity Press; 2008.
Sun-Edelstein C, Tepper SJ, Shapiro RE. Drug-induced serotonin syndrome: a review. Expert
Opinion Drug Safety 2008;7(5):587-96.
Wimbiscus M, Kostenkjo O, Malone D. MAO inhibitors: risks, benefits, and lore. Cleveland
Clinic J Med 2010;77(12):859-82.
69
The MAO Handbook
70
CME Posttest and Certificate
Release/Expiration Dates
Print Monograph Released: December 15, 2011
Electronic Books Released: January, 2012
CME Credit Expires : December 14, 2014. If this date has passed, please contact NEI for updated information.
CME Posttest Study Guide

PLEASE NOTE: The posttest can only be submitted online. The posttest questions have been provided below solely
as a study tool to prepare for your online submission. Faxed/mailed copies of the posttest cannot be processed and
will be returned to the sender. If you do not have access to a computer, contact customer service at 888-535-5600.
1. A 49-year-old man has been taking an MAO inhibitor for the past 5 years to manage his depression.
When he and his wife went out to dinner for their 30th anniversary he had two glasses of Chianti and
an Italian meal high in cheese content. He began to experience palpitations, sweating, nausea, vomiting
and extremely elevated blood pressure. His wife rushed him to the ER, where the doctors asked what
medications he is currently taking. Which of the following could be responsible for these symptoms?
A. Oral low-dose selegiline (10 mg/day)
B. Transdermal selegiline (6 mg/day)
C. Tranylcypromine (30 mg/day)
D. A and C
E. A, B, and C
2. A 32-year-old man takes an MAO inhibitor for social anxiety disorder and is otherwise healthy. He has a
bad cold that is keeping him up at night and wants to know if there is anything he can take to alleviate
the cold symptoms. Which of the following would be the safest medication to recommend?
A. Antihistamine without serotonin reuptake inhibition
B. Antihistamine with serotonin reuptake inhibition
C. None of these are safe
3. A 35-year-old woman on an MAO inhibitor experiences a medical emergency requiring immediate
surgery. Which of the following can generally be used with caution in this type of situation?
A. Benzodiazepine
B. Codeine
C. Morphine
D. Any of these can be used
E. None of these can be used
4. A 45- year-old man with severely treatment-resistant depression has exhibited a partial response to
a MAO inhibitor. Which of the following should absolutely NOT be used as an augmenting agent for this
patient?
A. Amitriptyline
B. Clomipramine
C. Nortriptyline
D. Protriptyline
71
The MAO Handbook
5. A 54-year-old man with a history of treatment-resistant depression has been successfully treated with
a monoamine oxidase inhibitor (MAOI) for the last year. He recently suffered a severe back injury and is
in quite a bit of pain. In light of potential interactions with the MAOI, which of the following would be an
acceptable pain management option for this patient?
A. Meperidine
B. NSAID
C. Tramadol
D. The patient cannot take any of these medications
6. A 36-year-old man with depression has had three therapeutic trials of serotonin reuptake inhibitors
(SRI) with notable improvement. His clinician is now considering switching from his current SRI to an
MAO inhibitor. Which of the following is an appropriate switching strategy in this situation?
A. Cross-titrate SRI with MAO inhibitor
B. Discontinue SRI, then initiate MAO inhibitor
C. Discontinue SRI, then wait five half-lives before initiating MAO inhibitor
D. Discontinue SRI, then wait 14 days before initiating MAO inhibitor
CME Online Posttest and Certificate

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only online, by clicking the link found at the end of this electronic book or at www.neiglobal.com/CME (under
Book). If a passing score of 70% or more is attained (required to receive credit), you can immediately print
your certificate. There is no fee for CME credits for this activity. If you do not have access to a computer, contact
customer service at 888-535-5600.
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The MAO Handbook

PUBLISHED BY NEI PRESS, an imprint of NEUROSCIENCE EDUCATION INSTITUTE

NEUROSCIENCE EDUCATION INSTITUTE

Copyright 2011 Neuroscience Education Institute.

This publication is in copyright. Subject to statutory exception and to the provisions of

Printed in the United States of America

Typeset in Myriad Pro

Library of Congress Cataloging-in-Publication Data

Adobe PDF is either a registered trademark or trademark of Adobe Systems

Chapter 1: Monoamine Oxidase Inhibitors (MAOIs): The Basics..................................1

Chapter 2: Myth #1: The Tyramine Reaction.......................................................................11

Chapter 3: Myths #2 and #3: The Cold Medication/Stimulant Interaction..............23

Chapter 4: Myth #4: The Anesthetic Interaction................................................................31

Chapter 5: Myth #5: The Tricyclic Interaction.....................................................................37

Chapter 6: Myth #6: The Painkiller Interaction...................................................................43

Chapter 7: Myth #7: The Psychotropic Concomitant Medication Interaction........49

Chapter 8: MAOIs: Tips and Pearls..........................................................................................61

CME Posttest and Certificate....................................................................................................71

Accreditation and Credit Designation Statements

A certificate of participation for completing this activity will also be available.

Instructions for CME Credit

NEI Disclosure Policy

Individual Disclosure Statements

Stephen M. Stahl, MD, PhD

Disclosure of Off-Label Use

Identify foods that can or cannot be consumed by patients on different types

Monoamine Oxidase (MAO)

FIGURE 1.1. The first clinically effective antidepressants discovered were

TABLE 1.1. MAO is an enzyme that metabolizes monoamines as well as trace

This means that MAO-A inhibition increases serotonin, norepinephrine, and

FIGURE 1.3. The inhibition of MAO-B is not effective as an antidepressant.

MAO-A and MAO-B Inhibition:

Monoamine Oxidase Inhibitors

TABLE 1.2. Currently available MAO inhibitors include phenelzine,

so if you go to pizza parties or wine and

unless you plan to eat more than 25 pieces of

The Pharmacology (cont.)

The Pharmacology (cont.)

TABLE 2.1. It may take as little as 10 mg of dietary tyramine to increase blood

The Owners Manual:

TABLE 2.2. Because of the potential danger of a hypertensive crisis from

Reversible Monoamine Oxidase A

Transdermal Delivery of Selective

How Much Tyramine Is Dangerous

FIGURE 2.6. A meal that contains 40 mg of tyramine is considered high in this

You cant take stimulants with MAOIs, so

You should completely avoid combining an

FIGURE 3.1. Decongestants that stimulate postsynaptic alpha-1 receptors, such as

The Owners Manual:

Stimulants are useful as bridging medications when starting or stopping MAOIs

Drug Interaction Data:

TABLE 3.2. Small, open-label studies have been conducted to investigate

The Owners Manual:

You should completely avoid combining an

The Owners Manual:

TABLE 5.1. The only tricyclic antidepressant to be strictly avoided in combination

Cyclobenzaprine, carbamazepine, and oxcarbazepine can be used with caution

Methadone and tramadol are weak serotonin

Tapentadol is a norepinephrine reuptake

The Owners Manual:

TABLE 6.1. There is no interaction between MAOIs and opioid mechanisms;

Besides, you cannot get there from here

You should completely avoid combining an

The Owners Manual: