Drug Comparison
For educational purposes only — a decision-support tool, not a substitute for clinical judgment.
Side-by-side rubric across 96 psychiatric medications. Every rating traces to a verbatim primary-source quote — click any cell to see it.
How to read this tool ▾
Rating scale
– Favorable / lower than class baseline
± Minimal / equivocal
+ Low / uncommon
++ Moderate / common
+++ High / very common
++++ Very high / class-outlier
Frequency vs severity
F = frequency, S = severity. Each gets its own pill colored on the same traffic-light scale: green → blue → yellow → orange → red. Click any cell for incidence percentages and NNH.
Evidence tier
A Network meta-analysis / RCT / FDA label
B Cohort / registry / pooled label data
C Expert review / textbook / case series
Sourcing
Click any cell to see the verbatim source quote and citation. Missing data shows n/a.
Data depth
++ Graded — frequency + severity, primary-source traces
+ FDA label — §6 frequency only (dashed border). Click for sub-types.
Blank — not yet checked (not “absent”)
–±++++++++++ABCF = frequency · S = severity · Dashed border = FDA label only · Click cell for details
⚠ Cross-class comparison (SSRI vs SNRI) — class floors may not apply uniformly.
4 drugs selected — Escitalopram, Sertraline, Venlafaxine, Duloxetine(click to collapse)
4/4 selected
Escitalopram
Lexapro
Selective Serotonin Reuptake Inhibitor
FDA-approved indications
- Major depressive disorder — acute and maintenance (adults; adolescents 12–17 years)
- Generalized anxiety disorder — acute treatment (adults)
Off-label uses
- Panic disorder
- OCD
- PTSD
Half-life27 to 32 hours
Sertraline
Zoloft
Selective Serotonin Reuptake Inhibitor
FDA-approved indications
- Major depressive disorder (adults)
- Obsessive-compulsive disorder (adults; pediatric 6–17 years)
- Panic disorder, with or without agoraphobia (adults)
- Posttraumatic stress disorder (adults)
Off-label uses
- Generalized anxiety disorder
- Binge eating disorder
- Body dysmorphic disorder
Half-life26 hours
Venlafaxine
Effexor
Serotonin-Norepinephrine Reuptake Inhibitor
FDA-approved indications
- Major depressive disorder (adults)
- Generalized anxiety disorder (adults)
- Social anxiety disorder (adults)
- Panic disorder, with or without agoraphobia (adults)
Off-label uses
- Social anxiety disorder
- Panic disorder
- PTSD
Half-life5 hours (ODV active metabolite: 11 hours)
Duloxetine
Cymbalta · Duloxetine Delayed-Release · Irenka
Serotonin-Norepinephrine Reuptake Inhibitor
FDA-approved indications
- Major depressive disorder (adults)
- Generalized anxiety disorder (adults; pediatric 7+)
- Diabetic peripheral neuropathic pain (adults)
- Fibromyalgia (adults; pediatric 13+)
Off-label uses
- Stress urinary incontinence
- Chemotherapy-induced neuropathy
Half-life12 hours
Decision GuideWhen to pick each / when to consider an alternative
Escitalopram
Consider when
- First-line MDD where efficacy and tolerability both matter — only SSRI ranking top-tier on both axes in Cipriani 2018 NMA
- Generalized anxiety disorder — FDA-approved for both MDD and GAD; citalopram is MDD-only
- Adolescent depression (age 12+) — one of only two SSRIs with FDA-approved pediatric MDD indication (with fluoxetine)
- Polypharmacy with CYP2D6 or CYP3A4 substrates — minimal CYP inhibition; safest SSRI for drug interactions alongside citalopram
- +1 more
Consider an alternative when
- Sexual dysfunction is treatment-limiting — highest-SD SSRI in Reichenpfader 2014 NMA; significant vs bupropion, fluoxetine, mirtazapine
- QTc prolongation risk — dose-dependent QTc increase; max 10 mg in elderly, hepatic impairment, or CYP2C19 PM
- CYP2C19 poor metabolizer — 2× plasma levels in PMs; max 10 mg may limit therapeutic dose optimization
- Cost is primary constraint — marginally more expensive than citalopram or sertraline generics in some formularies
- +1 more
Sertraline
Consider when
- Cardiac comorbidity or post-ACS depression — only SSRI with prospective trial evidence for cardiac safety (SADHART, ENRICHD)
- Postpartum depression or breastfeeding — lowest infant relative dose among SSRIs; specifically recommended first-line in lactation
- Polypharmacy with CYP2D6 substrates — mild 2D6 inhibition (~30% desipramine AUC increase) vs 300–400% with fluoxetine/paroxetine
- PMDD requiring dosing flexibility — only SSRI with FDA label supporting both continuous and luteal-phase dosing strategies
- +1 more
Consider an alternative when
- Diarrhea-prone or IBS patient — class-top labeled diarrhea 20% vs 10% placebo; OR 2.10 vs escitalopram in Cochrane NMA
- Sexual dysfunction is treatment-limiting — class-top orgasm dysfunction 45.6% (Serretti 2009); higher than escitalopram or fluvoxamine
- Top-tier MDD efficacy is the priority — mid-tier in Cipriani 2018 NMA; below escitalopram, paroxetine, and vortioxetine
- QTc risk factors present — FDA TQT showed mean ΔQTc 10 ms at 2× max dose; pimozide contraindicated
- +1 more
Venlafaxine
Consider when
- Treatment-resistant depression or SSRI non-response — top-tier efficacy in Cipriani 2018 NMA; ~6% remission advantage over SSRIs
- Depression with comorbid anxiety disorders — FDA-approved for GAD, SAD, and panic disorder alongside MDD
- Ascending dose-response needed — dose-dependent NE engagement above 150 mg allows titration from SSRI-like to full SNRI effect
- Pain comorbidity with depression — noradrenergic effects at higher doses assist with pain; though duloxetine has FDA pain indications
- +1 more
Consider an alternative when
- Adherence may falter — worst discontinuation syndrome among SNRIs (incidence 0.40, Henssler 2024); withdrawal within 24–48 h of missed dose
- Sexual dysfunction is a concern — total SD OR 24.82 (Serretti 2009); highest SD risk among commonly prescribed antidepressants in Danish cohort
- Uncontrolled or borderline hypertension — dose-dependent BP elevation especially >150 mg; most pronounced BP effect among SNRIs
- Overdose risk present — cardiotoxicity in overdose; UK regulatory CI for heart disease; higher toxicity index than SSRIs
- +1 more
Duloxetine
Consider when
- Chronic pain comorbidity with depression — only SNRI FDA-approved for DPNP, fibromyalgia, and chronic MSK pain; single agent treats both
- Balanced SNRI effect from starting dose — 10:1 SERT:NET ratio provides dual reuptake inhibition at 30–60 mg without venlafaxine's dose threshold
- Pediatric anxiety or fibromyalgia — unique FDA approvals for GAD (≥7 years) and fibromyalgia (≥13 years) among SNRIs
- Functional impairment is the primary target — ranks second among antidepressants for SDS functional improvement
- +1 more
Consider an alternative when
- Active hepatic disease or chronic alcohol use — FDA hepatotoxicity warning unique among SNRIs; contraindicated in liver disease/cirrhosis
- Emotional blunting is a concern — 75% prevalence (Goodwin 2017), +29 percentage points above SSRI cluster; leading switch reason
- CYP2D6 substrates co-prescribed — moderate CYP2D6 inhibitor unique among SNRIs; desipramine AUC +122%
- On CYP1A2 inhibitor (fluvoxamine, ciprofloxacin) — AUC increase up to 460%; contraindication-level interaction
- +1 more
Drug-Drug Interactions2 contraindicated4 major
Educational reference only. Interactions are extracted from FDA prescribing information and DDInter 2.0. Always verify with institutional pharmacy systems before clinical decisions.
Efficacy & Acceptability (10 axes)— NMA efficacy & discontinuation data (not side effects)
| Axis | Escitalopram | Sertraline | Venlafaxine | Duloxetine |
|---|---|---|---|---|
| 📊 Efficacy (response rates) | ||||
MDDEfficacy | — | — | ||
GADEfficacy | — | — | ||
OCDEfficacy | — | — | ||
PTSDEfficacy | — | — | ||
SADEfficacy | — | — | ||
Panic DisorderEfficacy | — | — | ||
| 🛡️ Acceptability (all-cause discontinuation) | ||||
MDDAcceptability | — | — | ||
GADAcceptability | — | — | ||
SADAcceptability | — | — | ||
Panic DisorderAcceptability | — | — | ||
| Axis | Escitalopram SSRI | Sertraline SSRI | Venlafaxine SNRI | Duloxetine SNRI |
|---|---|---|---|---|
| Boxed Warnings | ||||
Suicidality (boxed warning) | ||||
Mania / hypomania induction | — | — | ||
| CNS | ||||
Sedation / somnolence | ||||
Activation / insomnia | ||||
Emotional blunting | ||||
Seizure risk | ||||
| Metabolic | ||||
Weight gain | — | — | ||
Weight loss | — | — | ||
Metabolic (glucose / lipids) | — | — | ||
| Autonomic | ||||
Anticholinergic burden | ||||
Urinary retention / hesitancy | — | — | — | |
Orthostatic hypotension | — | |||
Sweating | ||||
Angle-closure glaucoma | ||||
| Cardiac | ||||
QTc prolongation | ||||
Blood pressure elevation | — | — | — | |
Heart rate / tachycardia | — | — | ||
| GI | ||||
Nausea / GI (general) | ||||
| Hepatic | ||||
Liver enzymes / hepatotoxicity | — | — | ||
| Electrolytes | ||||
Hyponatremia / SIADH | ||||
| Sexual | ||||
Sexual dysfunction | ||||
| Discontinuation | ||||
Withdrawal / discontinuation | ||||
| Interactions | ||||
Serotonin syndrome risk | ||||
CYP interactions / DDI profile | ||||
| Safety | ||||
Bleeding risk | ||||
Overdose toxicity | — | |||
| Pregnancy | ||||
Teratogenicity | — | |||
Lactation / breastfeeding safety | — | |||