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Best Serotonin and Norepinephrine Reuptake Inhibitor for major depressive disorder

Top-rated pick: Fetzima — pharmaranks score 72/100, the highest of the 8 Serotonin and Norepinephrine Reuptake Inhibitor drugs used for major depressive disorder, ranked by our independent FDA recall-safety score. Compare them with all treatments for major depressive disorder or the full Serotonin and Norepinephrine Reuptake Inhibitor class. Not medical advice — always consult a professional.

Quick answer: Of the 8 serotonin and norepinephrine reuptake inhibitor drugs we rate for major depressive disorder, 6 are available as lower-cost generics, and most are capsule. Our ranking reflects each drug’s FDA recall-safety record — not clinical effectiveness for major depressive disorder; the right choice depends on your situation, so confirm it with your prescriber.

Rated against independent regulatory sources·Last updated August 17, 2026·How we rate

How serotonin and norepinephrine reuptake inhibitor work

SNRIs slow the reabsorption of two brain chemicals, serotonin and norepinephrine, back into nerve cells. This leaves more of both available in the gaps between neurons to keep signaling, which can improve mood, anxiety, and certain types of chronic pain.

Source: Duloxetine - StatPearls - NCBI Bookshelf

Other drug classes for major depressive disorder

Top serotonin and norepinephrine reuptake inhibitor for major depressive disorder: 1. Fetzima · 2. Levomilnacipran Hydrochloride · 3. Savella

Best-rated Serotonin and Norepinephrine Reuptake Inhibitor for major depressive disorder, ranked by pharmaranks score
#DrugRatingPharmacy pays
172/100View →
272/100View →
372/100$97View →
470/100$115View →
5Not yet rated$3View →
6Not yet rated$3View →
7Not yet rated$97View →
8Not yet rated$115View →

Full ranking · 8 drugs

ABBVIE logo
#1 of 5 in Serotonin and Norepinephrine Reuptake Inhibitor

fetzima

Boxed warning

PrescriptionFDA-sourced

72/100

Fetzima (Levomilnacipran Hydrochloride) is a serotonin and norepinephrine reuptake inhibitor used to treat Major Depressive Disorder.

(6 data points)
serotonin and norepinephrine reuptake inhibitormajor depressive disorder

Price varies

View details →
#1 of 5 in Serotonin and Norepinephrine Reuptake Inhibitor

levomilnacipran hydrochloride

PrescriptionFDA-sourced

72/100

Levomilnacipran Hydrochloride is a serotonin and norepinephrine reuptake inhibitor used to treat Major Depressive Disorder.

(8 data points)
serotonin and norepinephrine reuptake inhibitormajor depressive disorder

Price varies

View details →
ABBVIE logo
#1 of 5 in Serotonin and Norepinephrine Reuptake Inhibitor

savella

Boxed warning

PrescriptionFDA-sourced

72/100

Savella (Milnacipran Hydrochloride) is a serotonin and norepinephrine reuptake inhibitor used to treat Major Depressive Disorder.

(6 data points)
serotonin and norepinephrine reuptake inhibitormajor depressive disorder

Pharmacy pays

From ~$10.88/30· 3 forms Save up to 96% in class
View details →

desvenlafaxine succinate

Boxed warning

PrescriptionFDA-sourced

70/100

Desvenlafaxine Succinate is a serotonin and norepinephrine reuptake inhibitor used to treat Major Depressive Disorder.

(3 data points)
serotonin and norepinephrine reuptake inhibitormajor depressive disorder

Pharmacy pays

From ~$114.94/30· 2 forms Save up to 97% in class
View details →

cymbalta

PrescriptionFDA-sourced

New

Cymbalta (Duloxetine Hydrochloride) is a serotonin and norepinephrine reuptake inhibitor used to treat Anxiety Disorders, Major Depressive Disorder, Diabetic Neuropathies, Musculoskeletal Pain.

serotonin and norepinephrine reuptake inhibitoranxiety disordersmajor depressive disorder

Pharmacy pays

From ~$2.86/30· 4 forms
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drizalma sprinkle

Boxed warning

PrescriptionFDA-sourced

New

Drizalma Sprinkle (Duloxetine Hydrochloride) is a serotonin and norepinephrine reuptake inhibitor used to treat Anxiety Disorders, Major Depressive Disorder, Diabetic Neuropathies, Musculoskeletal Pain.

serotonin and norepinephrine reuptake inhibitoranxiety disordersmajor depressive disorder

Pharmacy pays

From ~$2.86/30· 4 forms
View details →

milnacipran hydrochloride

Boxed warning

PrescriptionFDA-sourced

New

Milnacipran Hydrochloride is a serotonin and norepinephrine reuptake inhibitor used to treat Major Depressive Disorder.

serotonin and norepinephrine reuptake inhibitormajor depressive disorder

Pharmacy pays

From ~$10.88/30· 3 forms Save up to 96% in class
View details →

pristiq

Boxed warning

PrescriptionFDA-sourced

New

Pristiq (Desvenlafaxine Succinate) is a serotonin and norepinephrine reuptake inhibitor used to treat Major Depressive Disorder.

serotonin and norepinephrine reuptake inhibitormajor depressive disorder

Pharmacy pays

From ~$114.94/30· 2 forms Save up to 97% in class
View details →

Frequently asked

What is the best serotonin and norepinephrine reuptake inhibitor for major depressive disorder?
By our independent recall-safety rating — not an efficacy measure — fetzima ranks highest among Serotonin and Norepinephrine Reuptake Inhibitor drugs used for major depressive disorder. Always consult a professional.
Which serotonin and norepinephrine reuptake inhibitor drugs treat major depressive disorder?
pharmaranks lists 8 Serotonin and Norepinephrine Reuptake Inhibitor products used for major depressive disorder, 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.