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
4 drugs selected — Methylphenidate, Dexmethylphenidate, Amphetamine Mixed Salts, Lisdexamfetamine(click to collapse)
4/4 selected
Methylphenidate
Concerta · Methylin
CNS Stimulant (Methylphenidate-based) · C-II
FDA-approved indications
- ADHD (adults; pediatric 6+)
- Narcolepsy (adults; IR/ER formulations)
Off-label uses
- Narcolepsy
- Treatment-resistant depression (augmentation)
- Apathy in dementia
MechanismCentral Nervous System Stimulant
Half-life3 to 4 hours (d-methylphenidate)
Dexmethylphenidate
Focalin
CNS Stimulant (Methylphenidate-based) · C-II
FDA-approved indications
- ADHD (adults; pediatric 6+)
Off-label uses
- Narcolepsy
Half-life2 to 4.5 hours
Amphetamine Mixed Salts
Adderall · Dextroamphetamine Saccharate, Amphetamine Aspartate Monohydrate, Dextroamphetamine Sulfate, and Amphetamine Sulfate
CNS Stimulant (Amphetamine-based) · C-II
FDA-approved indications
- ADHD (adults; pediatric 6+)
- Narcolepsy (adults; IR formulation)
Off-label uses
- Narcolepsy
Half-life10 to 13 hours (d-amphetamine)
Lisdexamfetamine
Vyvanse
CNS Stimulant (Prodrug Amphetamine) · C-II
FDA-approved indications
- ADHD (adults; pediatric 6+)
- Moderate-to-severe binge eating disorder (adults)
Off-label uses
- Treatment-resistant depression (augmentation)
Half-life~1 hour (prodrug); d-amphetamine: 10 to 13 hours
Decision GuideWhen to pick each / when to consider an alternative
Methylphenidate
Consider when
- First-line ADHD treatment in children ≥6 — FDA-approved; APA/AAP-recommended alongside amphetamines as co-first-line
- Extensive formulation flexibility needed — IR, ER (Concerta, Ritalin LA), transdermal (Daytrana), liquid, chewable options
- Stimulant trial with lower abuse potential preferred — Schedule II but shorter duration may reduce diversion; transdermal patch option
- Comorbid tics — may be better tolerated than amphetamines in patients with tic disorders (MTA, PATS data)
- +1 more
Consider an alternative when
- Maximum efficacy is the priority — amphetamines show modestly larger effect sizes than methylphenidate in meta-analyses for adults
- Cardiovascular disease — class warning for sudden death, stroke, MI; baseline cardiac evaluation required
- Active substance use disorder — Schedule II controlled substance; abuse potential; non-stimulants may be safer
- Severe anxiety comorbidity — may worsen anxiety symptoms; atomoxetine or guanfacine may be preferred
- +1 more
Dexmethylphenidate
Consider when
- Methylphenidate non-response at lower doses — pure d-threo isomer is pharmacologically active form; 2× potency allows half the dose of racemic MPH
- Focalin XR for extended coverage — ER formulation with bimodal release; provides 10–12 hour coverage at half the racemic dose
- Reducing l-threo methylphenidate side effects — theoretically fewer peripheral NE-mediated cardiovascular effects from eliminating inactive l-isomer
Consider an alternative when
- Cost advantage of racemic methylphenidate — generic MPH ER is typically cheaper; clinical superiority of d-MPH over racemic MPH is not established
- Maximum amphetamine-class efficacy needed — effect sizes for amphetamines exceed methylphenidate class in adults (Lancet 2018)
- Cardiovascular disease — same class warnings as all stimulants; Schedule II controlled substance
- Active substance use disorder — same abuse potential as racemic methylphenidate; non-stimulants may be preferred
- +1 more
Amphetamine Mixed Salts
Consider when
- Maximum ADHD symptom reduction needed — largest effect sizes among all ADHD medications in adults (Lancet 2018 NMA)
- Methylphenidate non-response — ~40% of methylphenidate non-responders respond to amphetamines; class switch is standard practice
- Multiple formulation options — IR (Adderall), XR (Adderall XR), and lisdexamfetamine (prodrug) cover all dosing needs
- Narcolepsy — FDA-approved for narcolepsy alongside ADHD; useful when both conditions coexist
- +1 more
Consider an alternative when
- Active substance use disorder — highest abuse potential among stimulants; consider lisdexamfetamine (prodrug) or non-stimulants
- Cardiovascular disease or structural cardiac abnormality — class warning for sudden death; pre-treatment cardiac screening per guidelines
- Severe anxiety comorbidity — amphetamines may significantly worsen anxiety; non-stimulants preferred
- Tic disorder present — may exacerbate tics more than methylphenidate; guanfacine or clonidine may be better
- +1 more
Lisdexamfetamine
Consider when
- ADHD with abuse/diversion concern — prodrug (lysine-conjugated d-amphetamine) requires enzymatic cleavage; reduced abuse potential vs IR amphetamine
- Binge eating disorder — only stimulant FDA-approved for BED; reduces binge days/week in adults
- Smooth, extended coverage needed — prodrug pharmacokinetics provide consistent 12–14 hour coverage without peaks and troughs
- Adult ADHD where amphetamine class is preferred — large effect sizes consistent with mixed amphetamine salts
Consider an alternative when
- Cost is a primary constraint — brand-only pricing (Vyvanse); generic amphetamine salts or methylphenidate are far cheaper
- Cardiovascular disease — same class warnings as all amphetamines; sudden death, stroke, MI risk in structural cardiac disease
- Severe anxiety comorbidity — amphetamine-class anxiety exacerbation; non-stimulants may be preferred
- Flexible dosing granularity needed — capsule formulations only; cannot split tablets for fine dose adjustment
- +1 more
Drug-Drug Interactions1 major2 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 | Methylphenidate | Dexmethylphenidate | Amphetamine Mixed Salts | Lisdexamfetamine |
|---|---|---|---|---|
| 📊 Efficacy (response rates) | ||||
ADHDEfficacy⊘ | ||||
| 🛡️ Acceptability (all-cause discontinuation) | ||||
ADHDAcceptability | ||||
| Axis | Methylphenidate stimulant | Dexmethylphenidate stimulant | Amphetamine Mixed Salts stimulant | Lisdexamfetamine stimulant |
|---|---|---|---|---|
| Boxed Warnings | ||||
Mania / hypomania induction | ||||
Abuse / addiction liability | ||||
| CNS | ||||
Activation / insomnia | ||||
Seizure risk | ||||
Tics / Tourette's exacerbation | ||||
| Metabolic | ||||
Weight loss | — | — | ||
Appetite suppression / anorexia | ||||
| Pediatric | ||||
Growth suppression (pediatric) | ||||
| Autonomic | ||||
Dry mouth (xerostomia) | — | — | ||
Sweating | ||||
| Cardiac | ||||
Serious CV / sudden death (ADHD labeled axis) | — | — | ||
Blood pressure elevation | ||||
Heart rate / tachycardia | ||||
| Vascular | ||||
Peripheral vasculopathy / Raynaud's | ||||
| GI | ||||
Nausea / GI (general) | ||||
| Local | ||||
Application/injection-site reactions | — | — | — | |
| Sexual | ||||
Sexual dysfunction | — | — | — | |
| GU | ||||
Priapism | — | — | ||
| Discontinuation | ||||
Withdrawal / discontinuation | ||||
| Interactions | ||||
Serotonin syndrome risk | — | — | ||
MAOI co-administration contraindication | ||||
CYP interactions / DDI profile | ||||
| Safety | ||||
Overdose toxicity | ||||
| Pregnancy | ||||
Lactation / breastfeeding safety | ||||