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 — Aripiprazole, Paliperidone, Risperidone, Olanzapine(click to collapse)
4/4 selected
Aripiprazole
Abilify
Second-Generation Antipsychotic (Partial D2 Agonist)
FDA-approved indications
- Schizophrenia (adults; adolescents 13+)
- Irritability associated with autistic disorder (6–17 years)
- Tourette's disorder (6–18 years)
Off-label uses
- Bipolar depression (adjunct)
- Tic disorders
- Agitation in dementia
MechanismAtypical Antipsychotic
Half-life75 hours (dehydro-aripiprazole: 94 hours)
Paliperidone
Invega · INVEGA SUSTENNA
Second-Generation Antipsychotic
FDA-approved indications
- Schizophrenia (adults)
- Schizoaffective disorder — mono or adjunct to mood stabilizers/antidepressants (adults)
Off-label uses
- Bipolar disorder
- Agitation in dementia (limited direct evidence; extrapolated from risperidone data)
Half-life23 hours
Risperidone
Risperdal
Second-Generation Antipsychotic
FDA-approved indications
- Schizophrenia (adults; adolescents 13–17 years)
- Acute manic or mixed episodes in Bipolar I — mono or adjunct with lithium/valproate
- Irritability associated with autistic disorder (5–16 years)
Off-label uses
- PTSD
- OCD augmentation
- Agitation in dementia
MechanismAtypical Antipsychotic
Half-life3 hours (9-OH-risperidone: 21 hours)
Olanzapine
Zyprexa
Second-Generation Antipsychotic
FDA-approved indications
- Schizophrenia (adults; adolescents 13–17 years)
- Acute manic or mixed episodes in Bipolar I — mono or adjunct with lithium/valproate
- Bipolar I maintenance (adults)
- Treatment-resistant depression — combination with fluoxetine (adults)
Off-label uses
- Anorexia nervosa
- Chemotherapy-induced nausea
- Delirium
MechanismAtypical Antipsychotic
Half-life21 to 54 hours
Decision GuideWhen to pick each / when to consider an alternative
Aripiprazole
Consider when
- Hyperprolactinemia concern — only SGA that lowers prolactin; can reverse galactorrhea/amenorrhea from prior antipsychotic
- Metabolic-sparing antipsychotic needed — lowest BMI change (+0.22 kg/m²) and near-placebo glucose/lipid effects in Huhn 2019 NMA
- Pediatric autism irritability (6–17) or Tourette disorder — FDA-approved both; one of only two SGAs with pediatric autism indication
- LAI for long-term adherence — monthly Maintena or 2-monthly Asimtufii; broadest LAI option set among partial agonists
- +1 more
Consider an alternative when
- History of pathological gambling, hypersexuality, or impulse-control disorder — partial D2 agonism carries unique compulsive behavior risk
- Akathisia is poorly tolerated — Huhn 2019 RR ~1.95 (mid-to-high among SGAs); akathisia is leading discontinuation cause
- Restlessness, insomnia, or anxiety worsens with activation — partial-agonist activation profile worse than quetiapine/olanzapine
- Severe acute psychosis requiring rapid sedation — partial agonist may have slower onset; olanzapine IM or haloperidol IM preferred
- +1 more
Paliperidone
Consider when
- Hepatic impairment — 80% renal clearance minimizes hepatic metabolism; no dose adjustment for hepatic impairment
- CYP drug interaction burden is high — avoids CYP2D6/3A4 pathways that complicate risperidone, aripiprazole, and others
- Long-acting injection for non-adherence — three LAI formulations: monthly (Sustenna), 3-monthly (Trinza), 6-monthly (Invega Hafyera)
- Schizoaffective disorder — FDA-approved indication distinct from risperidone; broadest psychotic disorder coverage with LAI
- +1 more
Consider an alternative when
- Hyperprolactinemia concern — class-top prolactin elevation among SGAs; galactorrhea, amenorrhea, osteoporosis, sexual dysfunction
- GI structural narrowing (Crohn's, diverticular disease) — osmotic ER tablet shell may cause obstruction; ghost tablets in stool
- Severe renal impairment — primarily renally cleared; CrCl <50 mL/min requires dose reduction; not recommended CrCl <10
- Cost or formulary constraint — brand-only ER and LAI formulations at significant premium over generic risperidone
- +1 more
Risperidone
Consider when
- Pediatric autism irritability (5–16 years) — one of only two SGAs with FDA approval; most extensive pediatric data in autism
- Generic access and broad formulary coverage needed — well-established with extensive long-term outcome data
- LAI for non-adherent patient — biweekly Risperdal Consta; SQ Perseris monthly; established LAI track record
- Prolactin monitoring feasible — therapeutic window 28–112 ng/mL enables plasma-level-guided dosing
- +1 more
Consider an alternative when
- Hyperprolactinemia concern — class-near-top prolactin elevation; galactorrhea, amenorrhea, sexual dysfunction, osteoporosis risk
- Elderly patient with dementia — boxed warning for cerebrovascular events; risperidone specifically studied and flagged
- EPS-vulnerable patient — dose-dependent EPS; parkinsonism and TD risk higher than most newer SGAs
- Cardiometabolic risk patient — second-tier weight gain (~2 kg short-term); worse metabolic profile than aripiprazole/ziprasidone
- +1 more
Olanzapine
Consider when
- Acute agitation requiring rapid control — IM olanzapine for acute agitation; fastest onset among SGA IM formulations
- EPS-free profile critical — near-placebo akathisia (RR 0.99) and antiparkinson use (RR 1.02); avoids motor side effects
- Treatment-resistant depression adjunct — FDA-approved as Symbyax (olanzapine/fluoxetine) for TRD and bipolar depression
- Bipolar mania or maintenance — strong efficacy signal in Huhn 2019 NMA; FDA-approved for acute mania and maintenance
- +1 more
Consider an alternative when
- Cardiometabolic risk — class-top weight gain among non-clozapine SGAs (+3.82 kg Burschinski 2023); diabetes risk OR 1.67
- First-episode psychosis where metabolic baseline is preservable — early metabolic damage is poorly reversible; aripiprazole preferred
- BMI ≥25 or rapid weight gain history — labeled 30%+ weight gain ≥7% of body weight; appetite stimulation is near-universal
- Daytime sedation poorly tolerated — high H1 antagonism; dose-dependent somnolence limits functional recovery
- +1 more
Drug-Drug Interactions6 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 | Aripiprazole | Paliperidone | Risperidone | Olanzapine |
|---|---|---|---|---|
| 📊 Efficacy (response rates) | ||||
SchizophreniaEfficacy | ||||
| 🛡️ Acceptability (all-cause discontinuation) | ||||
SchizophreniaAcceptability | — | |||
| Axis | Aripiprazole SGA | Paliperidone SGA | Risperidone SGA | Olanzapine SGA |
|---|---|---|---|---|
| Boxed Warnings | ||||
Suicidality (boxed warning) | — | — | ||
Agranulocytosis / severe neutropenia | — | |||
Cerebrovascular events (elderly w/ dementia) | ||||
Impulse-control / pathological gambling | — | — | — | |
Neuroleptic malignant syndrome (NMS) | ||||
DRESS / multiorgan hypersensitivity | — | — | — | |
| CNS | ||||
Sedation / somnolence | ||||
Activation / insomnia | ||||
Akathisia / EPS | — | |||
Tardive dyskinesia | — | |||
Seizure risk | ||||
| Metabolic | ||||
Weight gain | ||||
Metabolic (glucose / lipids) | ||||
| Endocrine | ||||
Prolactin elevation | ||||
| Autonomic | ||||
Anticholinergic burden | ||||
Orthostatic hypotension | ||||
| Cardiac | ||||
QTc prolongation | ||||
Heart rate / tachycardia | — | — | — | |
| GI | ||||
Nausea / GI (general) | ||||
| Hepatic | ||||
Liver enzymes / hepatotoxicity | — | — | — | |
| Sexual | ||||
Sexual dysfunction | ||||
| GU | ||||
Priapism | — | — | ||
| Discontinuation | ||||
Withdrawal / discontinuation | — | — | — | |
| Interactions | ||||
CYP interactions / DDI profile | ||||
| Pregnancy | ||||
Teratogenicity | — | — | — | |
Lactation / breastfeeding safety | ||||
| Drug-specific / distinctive axes | ||||
Dysphagia (class warning) only in Paliperidone | — | — | — | |