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Industry: Email Alert RSS FeedAntidepressants and antiepileptic drugs for chronic non-cancer pain
American Family Physician, Feb 1, 2005 by Morris Maizels, Bill McCarberg
Strength of Recommendations
Key clinical recommendation Label References
Tricyclic antidepressants may be used for A 5, 8, 11, 21
treatment of chronic neuropathic and
non-neuropathic pain syndromes.
Tricyclic antidepressants are more B 6, 14
effective than SSRIs in the treatment of
neuropathic pain syndromes. An estimated
2.6 patients must be treated with tricyclic
antidepressants and 6.7 patients with SSRIs
to have one patient with more than 50
percent pain relief.
Serotoninergic antidepressants and currently B 7, 8, 30-33
approved antiepileptic drugs have little
documented efficacy and therefore should
not be used as first-line medications in
the treatment of non-neuropathic pain.
SSRIs = selective serotonin reuptake inhibitors.
A = consistent, good-quality patient-oriented evidence; B =
inconsistent or limited-quality patient-oriented evidence; C =
consensus, disease-oriented evidence, usual practice, opinion, or
case series. See page 409 for more information.
TABLE 1
Common Non-Cancer Pain Syndromes
Peripheral Central neuropathic Non-neuropathic
neuropathic pain pain pain *
Complex regional pain Multiple sclerosis Arthritis
syndrome Myelopathies Inflammatory
Human immunodeficiency Parkinson's disease arthritis
virus sensory neuropatl Poststroke pain Osteoarthritis
Idiopathic peripheral Chronic low back
neuropathy pain
Infection Chronic neck pain
Metabolic disorders Fibromyalgia
Alcohol and other toxins Post-traumatic
Diabetic neuropathy pain
Nutritional deficiencies
Nerve compression or
entrapment
Phantom limb pain
Postherpetic neuralgia
Trigeminal neuralgia
*--Elements of neuropathic pain may be superimposed on the
underlying disorder Information from reference 2..
TABLE 3
Antidepressants and Antiepileptic Drugs Used in Chronic Pain Syndromes
Drug Dosage
Antidepressants
Tricyclic antidepressants --
Amitriptyline (Elavil), * 10 to 25 mg at bedtime; increase by
imipramine (Tofranil) * 10 to 25 mg per week up to 75 to 150
mg at bedtime or a therapeutic drug
level.
Desipramine (Norpramin), * 25 mg in the morning or at bedtime;
nortriptyline (Pamelor) * increase by 25 mg per week up to 150
mg per day or a therapeutic drug
level.
Selective serotonin
reuptake inhibitors
Fluoxetine (Prozac), * 10 to 20 mg per day; up to 80 mg per
paroxetine (Paxil) * day for fibromyalgia.
Novel antidepressants
Bupropion (Wellbutrin) * 100 mg per day; increase by 100 mg
per week up to 200 mg twice daily
(400 mg per day).
Venlafaxine (Effexor) * 37.5 mg per day; increase by 37.5 mg
per week up to 300 mg per day.
Duloxetine (Cymbalta) * 20 to 60 mg per day taken once or
twice daily in divided doses (for
depression); 60 mg twice daily for
fibromyalgia
Antiepileptic drugs
First-generation agents
Carbamazepine (Tegretol) 200 mg per day; increase by 200 mg per
week up to 400 mg three times daily
(1,200 mg per day).
Phenytoin (Dilantin) * 100 mg at bedtime; increase weekly up
to 500 mg at bedtime.
Second-generation agents
Gabapentin (Neurontin) 100 to 300 mg at bedtime; increase by
100 mg every 3 days up to 1,800 to
3,600 mg per day taken in divided
doses three times daily.
Pregabalin (Lyrica) 150 mg at bedtime for diabetic
neuropathy; 300 mg twice daily for
postherpetic neuralgia.
Lamotrigine (Lamictal) * 50 mg per day; increase by 50 mg
every 2 weeks up to 400 mg per day.
Drug Side effects, contraindications, and
comments
Antidepressants
Tricyclic antidepressants Side effects: dry mouth, constipation,
urinary retention, sedation, weight
gain
Contraindications: cardiac conduction
abnormalities, recent cardiac
events, narrow-angle glaucoma
Amitriptyline (Elavil), * Tertiary amines have greater
imipramine (Tofranil) * anticholinergic side effects;
therefore, these agents should not
be used in elderly patients.
Desipramine (Norpramin), * Secondary amines have fewer
nortriptyline (Pamelor) * anticholinergic side effects.
Selective serotonin
reuptake inhibitors
Fluoxetine (Prozac), * Side effects: nausea, sedation,
paroxetine (Paxil) * decreased libido, sexual
dysfunction, headache, weight gain
Novel antidepressants Efficacy in pain syndromes is
relatively poor.
Bupropion (Wellbutrin) * Side effects: anxiety, insomnia or
sedation, weight loss, seizures (at
dosages above 450 mg per day)
Venlafaxine (Effexor) * Side effects: headache, nausea,
sweating, sedation, hypertension,
seizures
Serotoninergic properties in dosages
below 150 mg per day; mixed
serotoninergic and noradrenergic
properties in dosages above
150 mg per day
Duloxetine (Cymbalta) * Side effects: nausea, dry mouth,
constipation, dizziness, insomnia
Antiepileptic drugs
First-generation agents
Carbamazepine (Tegretol) Side effects: dizziness, diplopia,
nausea
Treatment can result in aplastic
anemia.
Phenytoin (Dilantin) * Side effects: dizziness, ataxia,
slurred speech, confusion, nausea,
rash
Treatment can result in blood
dyscrasias and hepatotoxicity.
Second-generation agents
Gabapentin (Neurontin) Side effects: drowsiness, dizziness,
fatigue, nausea, sedation, weight
gain
Pregabalin (Lyrica) Side effects: drowsiness, dizziness,
fatigue, nausea, sedation, weight gain
Lamotrigine (Lamictal) * Side effects: dizziness, constipation,
nausea; rarely, life-threatening
rashes
*--Not approved by the U.S. Food and Drug Administration for treatment
of neuropathic pain.
TABLE 4
Study-Quality Ratings for Antidepressants and Antiepileptic Drugs
in Chronic Pain Syndromes
Neuropathic pain
Diabetic
neuropathy or
Trigeminal postherpetic
Drug neuralgia neuralgia
Antidepressants
Amitriptyline (Elavil) (4-8) 1
Fluoxetine (Prozac) (9)
Bupropion (Wellbutrin) (10) 2
Venlafaxine (Effexor) (11) 2
Duloxetine (Cymbalta) (12,13) 1
Antiepileptics
First generation
Carbamazepine (Tegretol) (14) 1 3
Phenytoin (Dilantin) (14) 3
Second generation
Gabapentin (Neurontin) (15,16) 1
Lamotrigine (Lamictal) (17) * 3
Pregabalin (Lyrica) (18,19) ([dagger]) 2
Non-neuropathic pain
Low back or
Drug Fibromyalgia other pain
Antidepressants
Amitriptyline (Elavil) (4-8) 1 2
Fluoxetine (Prozac) (9) 3
Bupropion (Wellbutrin) (10)
Venlafaxine (Effexor) (11)
Duloxetine (Cymbalta) (12,13) 1
Antiepileptics
First generation
Carbamazepine (Tegretol) (14)
Phenytoin (Dilantin) (14)
Second generation
Gabapentin (Neurontin) (115,16)
Lamotrigine (Lamictal) (17) *
Pregabalin (Lyrica) (18,19) ([dagger]) 2
1 = good-quality patient-oriented evidence, 2 = limited-quality
patient-oriented evidence, 3 = other evidence. See page 0000 for
more information on ratings.
*--Efficacy of lamotrigine as an adjunct to carbamazepine
or phenytoin.
([dagger])--Investigational drug (approval pending from U.S. Food
and Drug Administration).
Information from references 4 through 19.
TABLE 5
Clinical Guidelines for the Treatment of Chronic Pain
All chronic pain
Use of a pain scale facilitates clinical evaluation of the
patient's response to a therapeutic drug trial.
An assessment of quality of life and activities of daily
living should be incorporated into the clinical evaluation
of the therapeutic drug trial.
Identification of psychiatric comorbidity may suggest the
use of an antidepressant for nonpain indications.
Neuropathic pain
A tricyclic antidepressant is the preferred initial
therapy if the patient has coexisting insomnia, anxiety,
or depression, or if cost is a consideration.
An antiepileptic drug (e.g., gabapentin [Neurontin]) is
preferred if the patient cannot tolerate the side effects
of tricyclic antidepressants, has cardiac
contraindications to the use of tricyclic antidepressants
(e.g., conduction abnormalities, recent cardiac event), or
is a "frail elder."
Titrate the selected medication to achieve clinical effect
or to the maximum tolerated dosage (see Table 3). With
gabapentin, if no effect is seen at a dosage of 1,800 mg
per day, discontinue the drug; if a partial effect occurs,
titrate the drug to a dosage of 2,400 to 3,600 mg per day.
Monitor response to treatment.
If monotherapy is tolerated but only partially effective,
combine an antidepressant with an antiepileptic drug.
If monotherapy is poorly tolerated or ineffective, choose
a first-line agent from a different medication class or
use a second-line agent (e.g., bupropion [Wellbutrin],
venlafaxine [Effexor]).
If pain relief remains inadequate, consider use of a
short-acting or long-acting opioid or tramadol (Ultram).
Non-neuropathic pain
Exercise is the primary therapy for chronic low back pain
and fibromyalgia.
Begin treatment of low back pain with a nonsteroidal
anti-inflammatory drug (not effective in the treatment of
fibromyalgia).
Consider use of a tricyclic antidepressant as a pain
adjuvant to promote sleep and alleviate muscle spasm.
In appropriately selected patients, consider use of a
short- or long-acting opioid or tramadol.
Empiric use of antiepileptic drugs such as gabapentin is
not justified by the current literature but is common
practice in pain clinics.
Information from reference 2.
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