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Antidepressants Used for Pain Management
Drug/principal mechanism of actionPain indicationsCommon dosing1Common side effectsSpecial considerations
  • Amitriptyline
  • Tertiary amine TCA
  • Serotonin and norepinephrine reuptake inhibitor
  • Chronic pain
  • Neuropathic pain2
  • Headache: treatment and prophylaxis
  • Postherpetic neuralgia: treatment and prophylaxis
  • 25 mg QHS to maximum 100 mg/day
Dry mouth, orthostatic hypotension, urinary retention, constipation, sedation, weight gain
  • Black box warning: increased risk of suicidality in patients younger than 24 years
  • Caution in the elderly, patients with CAD, after acute MI, seizure disorder, angle-closure glaucoma
  • Cardiac conduction effects. Prolonged QT if combined with cisapride
  • Increased drug levels with other CYP 450-2D6 inhibitors.3 Fatal in overdose
  • Serotonin syndrome when combined with SSRIs or MAOIs
  • Pregnancy Class C
  • Nortriptyline
  • Secondary amine TCA
  • Serotonin and norepinephrine reuptake inhibitor
  • Chronic pain2
  • Neuropathic pain2
  • Myofascial pain2
  • Burning mouth syndrome2
  • 25 mg QHS to maximum
  • 150 mg/day
Dry mouth, orthostatic hypotension, urinary retention, constipation, sedation, weight gain,4 etc.
  • Black box warning: increased risk of suicidality in patients younger than 24 years
  • Caution in the elderly, patients with CAD. Cardiac conduction effects including prolonged QT
  • Drug interactions with other CYP 450-2D6 inhibitor drugs.3 Fatal in overdose
  • Serotonin syndrome
  • Pregnancy Class C
Duloxetine
  • Serotonin and norepinephrine reuptake inhibitor
  • Weak inhibitor of dopamine reuptake
  • Diabetic neuropathy5
  • Fibromyalgia5
  • Chronic musculoskeletal pain5
  • Start at 30 mg/day
  • Maximum 60 mg/day (for pain)
Nausea, xerostomia, constipation, insomnia, somnolence, fatigue, etc.
  • Black box warning: increased risk of suicidality in patients younger than 24 years
  • Duloxetine is not FDA approved for use in children
  • Withdrawal syndrome
  • Serotonin syndrome
  • Pregnancy Class C
Venlafaxine
  • Serotonin and norepinephrine reuptake inhibitor
  • Weak inhibitor of dopamine reuptake
  • Neuropathic pain5
  • Tension-type headache: prophylaxis5
  • 37.5 mg q day or BID
  • Maximum 225 mg/day
Somnolence, dizziness, nervousness, headache, nausea, sweating, etc.
  • Black box warning: increased risk of suicidality in patients younger than 24 years
  • Withdrawal syndrome
  • Caution in patients with seizure history, elderly, CV risk factors,6 etc.
  • Serotonin syndrome
  • Pregnancy Class C

Note: SSRIs and other SNRIs not found to be effective for neuropathic pain; therefore, not included in this table.

1Starting at low doses and slow titration were found to reduce most adverse effects and common side effects of antidepressants used in pain management.

2Off-label usage.

3Drugs such as methadone, protease inhibitors, cimetidine, cocaine, fluoxetine, paroxetine, sertraline, bupropion can cause increased levels of TCAs.

4Secondary amine tricyclics have fewer reported adverse effects, such as anticholinergic side effects, compared with tertiary amine tricyclic antidepressants.

5FDA approved.

6Less commonly, cardiac conduction abnormalities and hypertension have been reported.

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Anticonvulsants Used for Pain Management
Drug/principal mechanism of actionPain indicationsCommon dosing1Common side effectsSpecial considerations
  • Carbamazepine
  • Sodium channel blockade
  • Trigeminal neuralgia2
  • Glossopharyngeal neuralgia2
  • Neurogenic pain4
  • Pain4
  • Restless legs ...

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