What is the best tricyclic antidepressant for pain?

By our independent recall-safety rating — not an efficacy measure — anafranil ranks highest among Tricyclic Antidepressant drugs used for pain. Always consult a professional.

Which tricyclic antidepressant drugs treat pain?

pharmaranks lists 4 Tricyclic Antidepressant products used for pain, per NIH RxClass drug-classification data — each independently rated and ranked above.

How are these ranked?

By our independent score, currently based on FDA regulatory recall-safety data (the methodology blends additional sources as they come online). See the How we rate page.

Best Tricyclic Antidepressant for pain

Top-rated pick: Anafranil — pharmaranks score 70/100, the highest of the 4 Tricyclic Antidepressant drugs used for pain, ranked by our independent FDA recall-safety score. Compare them with all treatments for pain or the full Tricyclic Antidepressant class. Not medical advice — always consult a professional.

Quick answer: Of the 4 tricyclic antidepressant drugs we rate for pain, all are available as lower-cost generics, and most are tablet. Our ranking reflects each drug’s FDA recall-safety record — not clinical effectiveness for pain; the right choice depends on your situation, so confirm it with your prescriber.

Rated against independent regulatory sources·Last updated August 20, 2026·How we rate

Other drug classes for pain

Best opioid agonist Best muscle relaxant Best amide local anesthetic Best ester local anesthetic Best partial opioid agonist Best cyclooxygenase inhibitor Best general anesthetic Best central alpha-2 adrenergic agonist

Top tricyclic antidepressant for pain: 1. Anafranil · 2. Imipramine Hydrochloride · 3. Amitriptyline Hydrochloride

Best-rated Tricyclic Antidepressant for pain, ranked by pharmaranks score
#	Drug	Rating	Type	Form	Generic?	Pharmacy pays
1	Anafranil Boxed warning	70/100	Prescription	Capsule	Generic	$7	View →
2	Imipramine Hydrochloride Boxed warning	70/100	Prescription	Tablet	Generic	$3	View →
3	Amitriptyline Hydrochloride Boxed warning	68/100	Prescription	Tablet	Generic	$3	View →
4	Zonalon	66/100	Prescription	Topical	Generic	$5	View →

Full ranking · 4 drugs

#2 of 16 in Tricyclic Antidepressant

anafranil

Boxed warning

PrescriptionFDA-sourced

70/100

Anafranil (Clomipramine Hydrochloride) is a tricyclic antidepressant used to treat Depressive Disorder, Obsessive-Compulsive Disorder, Pain, Panic Disorder.

(1 data points)

tricyclic antidepressantdepressive disorderobsessive-compulsive disorder

Pharmacy pays

From ~$5.96/30· 3 forms Save up to 65% in class

View details →

#2 of 16 in Tricyclic Antidepressant

imipramine hydrochloride

Boxed warning

PrescriptionFDA-sourced

70/100

Imipramine Hydrochloride is a tricyclic antidepressant used to treat Attention Deficit Disorder with Hyperactivity, Depressive Disorder, Enuresis, Pain.

(5 data points)

tricyclic antidepressantattention deficit disorder with hyperactivitydepressive disorder

Pharmacy pays

From ~$2.28/30· 3 forms

View details →

amitriptyline hydrochloride

Boxed warning

PrescriptionFDA-sourced

68/100

Amitriptyline Hydrochloride is a tricyclic antidepressant used to treat Depressive Disorder, Pain.

(23 data points)

tricyclic antidepressantdepressive disorderpain

Pharmacy pays

From ~$1.02/30· 6 forms Save up to 6% in class

View details →

zonalon

PrescriptionFDA-sourced

66/100

Zonalon (Doxepin Hydrochloride) is a tricyclic antidepressant used to treat Anxiety Disorders, Depressive Disorder, Atopic Dermatitis, Pain.

(37 data points)

tricyclic antidepressantanxiety disordersdepressive disorder

Pharmacy pays

From ~$2.38/30· 8 forms Save up to 47% in class

View details →

Frequently asked

What is the best tricyclic antidepressant for pain?: By our independent recall-safety rating — not an efficacy measure — anafranil ranks highest among Tricyclic Antidepressant drugs used for pain. Always consult a professional.
Which tricyclic antidepressant drugs treat pain?: pharmaranks lists 4 Tricyclic Antidepressant products used for pain, per NIH RxClass drug-classification data — each independently rated and ranked above.
How are these ranked?: By our independent score, currently based on FDA regulatory recall-safety data (the methodology blends additional sources as they come online). See the How we rate page.