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 (NDRI vs SNRI vs NaSSA vs SMS) — class floors may not apply uniformly.
4 drugs selected — Bupropion, Venlafaxine, Mirtazapine, Vortioxetine(click to collapse)
4/4 selected
Bupropion
Wellbutrin · Forfivo
Norepinephrine-Dopamine Reuptake Inhibitor
FDA-approved indications
- Major depressive disorder (adults)
- Seasonal affective disorder — prevention (adults; XL only)
Off-label uses
- ADHD
- Sexual dysfunction (SSRI-induced)
- Weight loss (adjunct)
Half-life21 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)
Mirtazapine
Remeron · Mirataz
Noradrenergic and Specific Serotonergic Antidepressant
FDA-approved indications
- Major depressive disorder (adults)
Off-label uses
- Insomnia
- Appetite stimulation/weight gain
- Nausea (chemotherapy or other)
Half-life20 to 40 hours
Vortioxetine
Trintellix
Serotonin Modulator and Stimulator
FDA-approved indications
- Major depressive disorder (adults)
Off-label uses
- Generalized anxiety disorder
- Cognitive dysfunction in MDD
Half-life66 hours
Decision GuideWhen to pick each / when to consider an alternative
Bupropion
Consider when
- Sexual dysfunction on SSRIs/SNRIs is intolerable — only non-serotonergic first-line AD; placebo-level SD (~10%); also treats SSRI-induced SD as augmentation
- Weight gain is unacceptable — modest weight loss (−0.79 kg) or neutrality vs SSRIs/mirtazapine; no appetite stimulation
- Smoking cessation needed alongside depression — FDA-approved for both MDD and smoking cessation (Zyban); also component of Auvelity (DXM/bupropion)
- Apathy, psychomotor retardation, or fatigue predominates — dopaminergic/noradrenergic activation targets these symptoms directly
- +1 more
Consider an alternative when
- Active or recent eating disorder (anorexia, bulimia) — contraindicated; dose-dependent seizure risk elevated in this population
- Seizure disorder or seizure risk factors — contraindicated; highest seizure rate among first-line ADs; 450 mg/day ceiling reflects this
- Comorbid anxiety disorder is dominant — may worsen anxiety; insomnia 11–16%, agitation 3–9%; SSRIs/SNRIs preferred for anxious depression
- Insomnia-predominant depression — activating profile worsens sleep; consider mirtazapine, trazodone, or low-dose doxepin adjunct
- +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
Mirtazapine
Consider when
- Insomnia-predominant depression — improves total sleep time, slow-wave sleep (N3), and efficiency without REM suppression
- Underweight, cachectic, or anorectic patient — weight gain (+0.87 kg/8 wk) and appetite stimulation (17% vs 2%) are therapeutic goals
- Sexual dysfunction on SSRIs/SNRIs — ~24% SD vs 58–73% with SSRIs; no serotonin reuptake inhibition mechanism
- Comorbid nausea or GI distress — 5-HT3 antagonism (antiemetic mechanism) causes significantly less nausea than SSRIs/SNRIs
- +1 more
Consider an alternative when
- Daytime sedation cannot be tolerated — somnolence 54% vs 18% placebo; leading discontinuation cause at 10.4%
- Weight gain is unacceptable — Pillinger 2025 +0.87 kg; FDA label weight gain 12% vs 2%, appetite increase 17% vs 2%
- Metabolic syndrome, diabetes, or obesity — sustained appetite/weight signal; bupropion or vortioxetine preferred metabolically
- Prior DRESS, SJS, TEN, or bullous reaction — contraindicated for re-exposure per FDA label
- +1 more
Vortioxetine
Consider when
- Cognitive symptoms predominate — only antidepressant with significant objective cognitive improvement (DSST, TMT-B; g = −0.23 to −0.29)
- SSRI-induced sexual dysfunction has been a barrier — multimodal 5-HT1A agonism offsets SERT-driven SD; no CSFQ difference from placebo at 5–10 mg
- Top-tier efficacy and acceptability both desired — dual top-tier in Cipriani 2018 alongside escitalopram
- Discontinuation risk is a concern — ~66 h half-life provides self-taper; can stop abruptly without severe withdrawal
- +1 more
Consider an alternative when
- Nausea sensitivity — dose-dependent rates 21–32% at 5–20 mg vs 9% placebo; leading discontinuation cause
- Cost or formulary constraint — brand-only pricing at significant premium over generic SSRIs
- On strong CYP2D6 inhibitor or PM genotype — max 10 mg in PMs; dose halving required with paroxetine/fluoxetine/bupropion
- Broad indication coverage needed — MDD-only FDA approval; no anxiety, OCD, PTSD, or PMDD indications
- +1 more
Drug-Drug Interactions1 contraindicated5 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 (1 axes)— NMA efficacy & discontinuation data (not side effects)
| Axis | Bupropion | Venlafaxine | Mirtazapine | Vortioxetine |
|---|---|---|---|---|
| 📊 Efficacy (response rates) | ||||
MDDEfficacy | — | — | — | |
| Axis | Bupropion NDRI | Venlafaxine SNRI | Mirtazapine NaSSA | Vortioxetine SMS |
|---|---|---|---|---|
| Boxed Warnings | ||||
Suicidality (boxed warning) | ||||
Mania / hypomania induction | — | — | — | |
Agranulocytosis / severe neutropenia | — | — | — | |
DRESS / multiorgan hypersensitivity | — | — | — | |
| CNS | ||||
Sedation / somnolence | ||||
Activation / insomnia | ||||
Emotional blunting | ||||
Seizure risk | ||||
| Metabolic | ||||
Weight gain | — | — | ||
Weight loss | — | — | ||
Metabolic (glucose / lipids) | — | — | ||
| Autonomic | ||||
Anticholinergic burden | — | |||
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 | ||||
| Dermatologic | ||||
Rash (including SJS/TEN, pruritus, hypersensitivity) | — | — | — | |
| Sexual | ||||
Sexual dysfunction | ||||
| Discontinuation | ||||
Withdrawal / discontinuation | ||||
| Interactions | ||||
Serotonin syndrome risk | — | — | ||
CYP interactions / DDI profile | — | |||
| Safety | ||||
Bleeding risk | — | — | ||
Overdose toxicity | — | — | — | |
| Pregnancy | ||||
Teratogenicity | — | — | — | |
Lactation / breastfeeding safety | ||||
| Drug-specific / distinctive axes | ||||
Cardiovascular (HR + BP — favorable) only in Vortioxetine | — | — | — | |