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 (NRI vs alpha-2-agonist vs SNRI-ADHD) — class floors may not apply uniformly.
4 drugs selected — Atomoxetine, Guanfacine, Viloxazine, Clonidine(click to collapse)
4/4 selected
Atomoxetine
Strattera
Selective Norepinephrine Reuptake Inhibitor
FDA-approved indications
- ADHD (adults; pediatric 6+)
Off-label uses
- Anxiety disorders with ADHD
- Binge eating disorder
Half-life5 hours
Guanfacine
Intuniv · Guanfacine extended-release
Alpha-2 Adrenergic Agonist
FDA-approved indications
- ADHD — mono or adjunct to stimulants (children/adolescents 6–17 years; ER formulation)
Off-label uses
- PTSD
- Tic disorders
- Anxiety disorders (pediatric)
Half-life17 hours
Viloxazine
QELBREE
Serotonin-Norepinephrine Modulating Agent
FDA-approved indications
- Attention-deficit/hyperactivity disorder (adults; pediatric 6+)
Off-label uses
- Anxiety disorders (with ADHD)
Half-life7 hours
Clonidine
Kapvay
Alpha-2 Adrenergic Agonist
FDA-approved indications
- ADHD — mono or adjunct to stimulants (children/adolescents 6–17 years; ER formulation)
Off-label uses
- PTSD nightmares
- Tic disorders
- Opioid withdrawal
Half-life12 to 16 hours
Decision GuideWhen to pick each / when to consider an alternative
Atomoxetine
Consider when
- ADHD with comorbid substance use disorder — non-scheduled; no abuse potential; preferred when stimulant diversion risk is high
- ADHD with comorbid anxiety — anxiolytic effect documented in trials; stimulants may worsen anxiety
- 24-hour ADHD coverage needed — continuous NRI effect without wearing-off; covers morning routine through sleep onset
- Tic disorder comorbidity — does not exacerbate tics; may improve ADHD symptoms without worsening Tourette's
- +1 more
Consider an alternative when
- Rapid ADHD symptom response needed — takes 4–6 weeks for full effect vs stimulant onset within hours
- Hepatic impairment — CYP2D6 substrate; dose reduction required in hepatic impairment; rare hepatotoxicity reported
- On potent CYP2D6 inhibitor (paroxetine, fluoxetine, bupropion) — levels increase 6–8× in PMs or with strong inhibitors
- Suicidal ideation risk in children/adolescents — boxed warning for increased SI in pediatric patients (0.4% vs 0%)
- +1 more
Guanfacine
Consider when
- ADHD with comorbid tics or Tourette syndrome — FDA-approved ADHD (ER, ages 6–17); improves both ADHD and tic symptoms
- Stimulant-induced insomnia or emotional lability — α2A agonism calms hyperarousal; useful adjunct to stimulants
- ADHD with comorbid oppositional behavior — evidence for reducing oppositional/conduct symptoms beyond ADHD core
- Hypertension comorbidity — antihypertensive mechanism provides dual benefit in ADHD patients with elevated BP
- +1 more
Consider an alternative when
- Hypotension or bradycardia risk — dose-dependent BP and HR reduction; syncope risk especially during titration
- Abrupt discontinuation likely — rebound hypertension with sudden cessation; must taper over 3–7 days
- Daytime sedation is problematic — somnolence 13–38% across doses; leading side effect; may impair school/work performance
- Maximum ADHD efficacy needed — effect sizes smaller than stimulants; typically adjunctive rather than monotherapy
- +1 more
Viloxazine
Consider when
- Pediatric ADHD (ages 6–17) — FDA-approved ER formulation; newest non-stimulant option with novel NRI + 5-HT modulation
- ADHD with comorbid anxiety — serotonergic component may benefit comorbid anxiety; non-stimulant avoids anxiety worsening
- Stimulant refusal or contraindication — non-scheduled alternative; no abuse potential
- Rapid onset for a non-stimulant — clinical improvement seen within 1 week in trials; faster than atomoxetine's 4–6 weeks
- +1 more
Consider an alternative when
- Adult ADHD — FDA-approved only for children/adolescents 6–17; adult use is off-label with limited data
- Somnolence is problematic — 11–16% across doses; may impair daytime function
- Nausea sensitivity — GI side effects (nausea, vomiting, decreased appetite) are common dose-dependent AEs
- Long-term data needed — newest agent with limited long-term safety and efficacy data compared to atomoxetine or guanfacine
- +1 more
Clonidine
Consider when
- ADHD adjunct to stimulants — Kapvay ER FDA-approved as ADHD adjunct and monotherapy (ages 6–17); proven add-on to stimulants
- ADHD with comorbid tics — α2 agonism benefits both ADHD and tic symptoms; CADDRA-recommended for this combination
- Stimulant-induced insomnia — bedtime dosing leverages sedative effect to improve sleep onset in stimulant-treated patients
- ADHD with comorbid aggression or emotional dysregulation — calms hyperarousal; evidence for reducing aggressive behavior
- +1 more
Consider an alternative when
- Hypotension risk — more hypotensive than guanfacine; α2A/B/C non-selective means broader cardiovascular effects
- Abrupt discontinuation likely — rebound hypertension more severe than guanfacine; mandatory gradual taper
- Daytime sedation problematic — more sedating than guanfacine; less α2A-selective means more non-specific sedation
- Maximum ADHD efficacy needed — effect sizes smaller than stimulants and possibly guanfacine for core ADHD symptoms
- +1 more
Drug-Drug Interactions2 moderate
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 (2 axes)— NMA efficacy & discontinuation data (not side effects)
| Axis | Atomoxetine | Guanfacine | Viloxazine | Clonidine |
|---|---|---|---|---|
| 📊 Efficacy (response rates) | ||||
ADHDEfficacy | ||||
| 🛡️ Acceptability (all-cause discontinuation) | ||||
GeneralAcceptability | — | — | ||
| Axis | Atomoxetine NRI | Guanfacine alpha-2-agonist | Viloxazine SNRI-ADHD | Clonidine alpha-2-agonist |
|---|---|---|---|---|
| Boxed Warnings | ||||
Suicidality (boxed warning) | — | — | ||
Mania / hypomania induction | — | — | ||
Abuse / addiction liability | — | |||
| CNS | ||||
Sedation / somnolence | ||||
Activation / insomnia | ||||
Seizure risk | — | — | — | |
Other neurologic effects | — | — | — | |
Dizziness | — | — | ||
Fatigue / lethargy | — | — | ||
| Metabolic | ||||
Weight gain | — | — | ||
Appetite suppression / anorexia | — | — | ||
| Autonomic | ||||
Urinary retention / hesitancy | — | — | — | |
Sweating | — | — | — | |
Angle-closure glaucoma | — | — | — | |
| Cardiac | ||||
QTc prolongation | ||||
Cardiac conduction / AV block | — | — | ||
Serious CV / sudden death (ADHD labeled axis) | — | — | — | |
Blood pressure elevation | ||||
Heart rate / tachycardia | ||||
| GI | ||||
Nausea / GI (general) | ||||
| Hepatic | ||||
Liver enzymes / hepatotoxicity | — | — | — | |
| Dermatologic | ||||
Rash (including SJS/TEN, pruritus, hypersensitivity) | — | — | — | |
| Sexual | ||||
Sexual dysfunction | ||||
| GU | ||||
Priapism | — | — | — | |
| Discontinuation | ||||
Withdrawal / discontinuation | — | — | — | |
Rebound hypertension (alpha2-agonist discontinuation) | — | — | ||
| Interactions | ||||
MAOI co-administration contraindication | — | — | — | |
CYP interactions / DDI profile | ||||
| Safety | ||||
Overdose toxicity | — | |||
| Pregnancy | ||||
Lactation / breastfeeding safety | ||||
| Drug-specific / distinctive axes | ||||
Pheochromocytoma (§4.4 CI) only in Atomoxetine | — | — | — | |