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2010 4:39PM

AMITRIPTYLINE
THERAPEUTICS If It Works
*
Migraine – goal is a 50% or greater reduction
Brands in migraine frequency or severity. Consider
*
Elavil, Triptafen, Tryptanol, Endep, Elatrol, tapering or stopping if headaches remit for
Tryptizol, Trepiline, Laroxyl, Saroten, Triptyl, more than 6 months or if considering
Redomex pregnancy
*
Neuropathic pain – the goal is to reduce pain
Generic? intensity and symptoms, but usually does
Yes not produce remission
*
Insomnia – continue to use if tolerated and
encourage good sleep hygiene

Class If It Doesn’t Work

*
Tricyclic antidepressant (TCA) *
Increase to highest tolerated dose
*
Migraine: address other issues, such as
Commonly Prescribed for medication-overuse, other coexisting
(FDA approved in bold) medical disorders, such as anxiety, and
*
Depression consider changing to another agent or
*
Migraine prophylaxis adding a second agent
*
Tension-type headache prophylaxis *
Chronic pain: either change to another agent
*
Diabetic neuropathy or add a second agent
*
Post-herpetic neuralgia *
Insomnia: if no sedation occurs despite
*
Peripheral neuropathy with pain adequate dosing, stop and change to
*
Back or neck pain another agent
*
Phantom limb pain
*
Fibromyalgia
Best Augmenting Combos
*
Bulimia nervosa
*
Insomnia
for Partial Response or
*
Anxiety Treatment-Resistance
*
Nocturnal enuresis
*
Migraine: For some patients, low-dose
*
Pseudobulbar affect polytherapy with 2 or more drugs may be
*
Arthritic pain better tolerated and more effective than high-
dose monotherapy. May use in combination
with AEDs, antihypertensives, natural
products, and non-medication treatments,
How the Drug Works such as biofeedback, to improve headache
*
Blocks serotonin and norepinephrine control
reuptake pumps increasing their levels *
Chronic pain: AEDs, such as gabapentin,
within hours, but antidepressant effect takes pregabalin, carbamazepine and capsaicin,
weeks. Effect is more likely related to mexiletine, are agents used for neuropathic
adaptive changes in serotonin and pain. Opioids are appropriate for long-term
norepinephrine receptor systems over time. use in some cases but require careful
It also has antihistamine properties which monitoring
most likely causes the sedation in treating
insomnia Tests
*
Check ECG for QT corrected (QTc)
How Long Until It Works prolongation at baseline and when
*
Migraines – effective in as little as 2 weeks, increasing dose, especially in those with a
but can take up to 3 months on a stable dose personal or family history of QTc
to see full effect prolongation, cardiac arrhythmia, heart
*
Neuropathic pain – usually some effect failure or recent myocardial infarction. If
within 4 weeks patient is on diuretics, measure potassium
*
Insomnia, anxiety, depression – may be and magnesium at baseline and periodically
effective immediately, but effects often with treatment
delayed 2 to 4 weeks

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(continued) AMITRIPTYLINE

ADVERSE EFFECTS (AEs) Dosage Forms

*
Tablets: 10, 25, 50, 75, 100 and 150 mg
How Drug Causes AEs
*
Anticholinergic and antihistaminic properties How to Dose
are causes of most common AEs. Blockade *
Initial dose 10–25 mg/day taken about 1
of alpha-adrenergic-1 receptor may cause hour before retiring. Effective range from
orthostasis and sedation 10–400 mg but typically 150 mg or less

Notable AEs
*
Constipation, dry mouth, blurry vision,
increased appetite, nausea, diarrhea,
heartburn, weight gain, urinary retention,
sexual dysfunction, sweating, itching, rash,
fatigue, weakness, sedation, nervousness,
restlessness
Dosing Tips
*
Start at a low dose, usually 10 mg, and titrate
up every few days as tolerated. Low doses
are often effective for pain even though they
are below the usual effective antidepressant
dose

Life-Threatening and Overdose

Dangerous AEs *
Cardiac arrhythmias and ECG changes; death
*
Orthostatic hypotension, tachycardia, QTc can occur. CNS depression, convulsions,
prolongation, and rarely death severe hypotension, and coma are not rare.
*
Increased intraocular pressure Patients should be hospitalized. Sodium
*
Paralytic ileus, hyperthermia bicarbonate can treat arrhythmias and
*
Rare activation of mania or suicidal ideation hypotension. Treat shock with vasopressors,
*
Rare worsening of existing seizure disorders oxygen, or corticosteroids

Weight Gain Long-Term Use

*
Common *
Safe for long-term use

unusual not unusual common problematic Habit Forming

*
No
Sedation
*
Common How to Stop
*
Taper slowly to avoid withdrawal, including
unusual not unusual common problematic rebound insomnia. Withdrawal usually lasts
less than 2 weeks. For patients with well-
What to Do About AEs controlled pain disorders, taper very slowly
*
For minor AEs, lower dose or switch to (over months) and monitor for recurrence of
another agent. If tiredness/sedation are symptoms
bothersome, change to a secondary amine
(i.e., nortriptyline). For serious AEs, lower Pharmacokinetics
dose and consider stopping *
Metabolized by CYP450 system, especially
CYP2D6, 1A2. Half-life 10–28 h and
Best Augmenting Agents for AEs metabolized to nortriptyline
*
Try magnesium for constipation. For
migraine, consider using with agents that
cause weight loss (i.e., topiramate)
Drug Interactions
*
CYP2D6 inhibitors (duloxetine, paroxetine,
fluoxetine, bupropion), cimetidine, and
DOSING AND USE valproic acid can increase drug
concentration
Usual Dosage Range *
Fluvoxamine, a CYP1A2 inhibitor, prevents
*
Migraine/Pain: 10–100 mg/day metabolism to nortriptyline and increases
*
Depression, anxiety: 50–150 mg/day amitriptyline concentrations

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AMITRIPTYLINE (continued)

*
Tramadol increases risk of seizures in
patients taking TCAs
*
Phenothiazines increase tricyclic levels Children and Adolescents
*
Enzyme inducers, such as rifamycin, *
Some data for children over 12 and an
smoking, phenobarbital can lower levels appropriate treatment for adolescents with
*
Use with clonidine has been associated with migraine, especially children with insomnia
increases in blood pressure and who are not overweight. In children less than
hypertensive crisis 12, most commonly used at low dose for
*
May reduce absorption and bioavailability of treatment of enuresis
levodopa
*
May alter effects of antihypertensive
medications and prolongation of QTc,
especially problematic in patients taking Pregnancy
drugs that induce bradycardia *
Category C. Crosses the placenta and may
*
Use together with anticholinergics can cause fetal malformations or withdrawal.
increase AEs (i.e., risk of ileus) Generally not recommended for the
*
Methylphenidate may inhibit metabolism and treatment of pain or insomnia during
increase AEs pregnancy. For patients with depression or
*
Use within 2 weeks of monoamine oxidase anxiety, selective serotonin reuptake
(MAO) inhibitors may risk serotonin inhibitors (SSRIs) may be safer than TCAs
syndrome
Breast Feeding
*
Some drug is found in breast milk and use
Other Warnings/ while breast feeding is not recommended
Precautions
*
May increase risk of seizure

Do Not Use THE ART OF NEUROPHARMACOLOGY

*
Proven hypersensitivity to drug or other
TCAs Potential Advantages
*
In acute recovery after myocardial infarction *
Proven effectiveness in multiple pain
or uncompensated heart failure disorders. Can treat insomnia and
*
In conjunction with antiarrhythmics that depression, which are common in patients
prolong QTc interval with chronic pain
*
In conjunction with medications that inhibit
CYP2D6 Potential Disadvantages
*
AEs are often greater than SSRIs or SNRIs
and many AEDs. More anticholinergic AEs
than other TCAs. Weight gain and sedation
SPECIAL POPULATIONS can be problematic
Renal Impairment
Primary Target Symptoms
*
Use with caution. May need to lower dose *
Headache frequency and severity
*
Reduction in neuropathic pain
Hepatic Impairment
*
Use with caution. May need to lower dose

Cardiac Impairment Pearls

*
Do not use in patients with recent myocardial *
In patients with chronic pain, offers relief at
infarction, severe heart failure, history of QTc doses below usual antidepressant doses,
prolongation, or orthostatic hypotension and can treat coexisting insomnia
*
For patients with significant anxiety or
Elderly depressive disorders, not as effective as
*
More sensitive to AEs, such as sedation, newer drugs with more AEs. Consider
hypotension. Start with lower doses treatment of depression or anxiety with

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another agent together with a low dose of
amitriptyline or other TCA for pain
*
TCAs can often precipitate mania in patients
with bipolar disorder. Use with caution
*
Despite interactions, expert psychiatrists
may use with MAO inhibitors for refractory
depression
*
Many patients do not improve. The number
of patients needed to treat for moderate pain
relief in neuropathic pain is 2–3
*
Increases non-REM sleep time and
decreases sleep latency
Suggested Reading
Bryson HM, Wilde MI. Amitriptyline. A review of
its pharmacological properties and therapeutic
use in chronic pain states. Drugs Aging
1996;8(6):459–76.
Silberstein SD, Goadsby PJ. Migraine: preventive
treatment. Cephalalgia 2002;22(7):491–512.
17 [14–17] 7.5.2010 4:39PM
(continued) AMITRIPTYLINE
*
Effective for nocturnal enuresis in children.
Usual dose is 25 mg for children 6–10 and
50 mg for those 11 and older
*
May be used to treat pathologic laughing or
crying due to forebrain disease at doses of
30–75 mg per day
*
Previously used for ADHD before new
treatments became available. May be useful
as an adjunct for patients with pain and
coexisting ADHD
*
TCAs may increase risk of metabolic
syndrome
Verdu B, Decosterd I, Buclin T, Stiefel F, Berney
A. Antidepressants for the treatment of chronic
pain. Drugs 2008;68(18):2611–32.
Zin CS, Nissen LM, Smith MT, O’Callaghan JP,
Moore BJ. An update on the pharmacological
management of post-herpetic neuralgia and
painful diabetic neuropathy. CNS Drugs
2008;22(5):417–42
17