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 (mood-stabilizer vs anticonvulsant-MS vs SGA) — class floors may not apply uniformly.
4 drugs selected — Lithium, Valproate, Olanzapine, Aripiprazole(click to collapse)
4/4 selected
Lithium
Lithobid
Mood Stabilizer
FDA-approved indications
- Bipolar I — acute manic and mixed episodes (7+ years; monotherapy)
- Bipolar I — maintenance treatment (7+ years; monotherapy)
Off-label uses
- Cluster headache prophylaxis
- Augmentation of antidepressants in MDD
- Aggression/self-harm
Half-life18 to 36 hours
Valproate
Depakote · Divalproex sodium
Anticonvulsant/Mood Stabilizer
FDA-approved indications
- Acute manic or mixed episodes in Bipolar I (adults)
- Complex partial seizures — mono or adjunct (adults; pediatric 10+)
- Simple and complex absence seizures (adults; pediatric)
- Multiple seizure types including absence — adjunct (adults; pediatric)
Off-label uses
- Agitation in dementia
- Impulse control disorders
- Neuropathic pain
Half-life9 to 16 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
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)
Decision GuideWhen to pick each / when to consider an alternative
Lithium
Consider when
- Bipolar mania — gold standard mood stabilizer with 60+ years of evidence; FDA-approved for acute mania and maintenance
- Anti-suicide benefit — only psychiatric medication with replicated evidence for reducing suicide risk across bipolar and MDD
- Bipolar maintenance preventing both mania and depression — strongest long-term relapse prevention data of any mood stabilizer
- Treatment-resistant depression augmentation — FDA-supported augmentation strategy; effective with SSRIs, SNRIs, and TCAs
- +1 more
Consider an alternative when
- Renal disease or progressive renal impairment — narrow therapeutic index with 95% renal excretion; nephrotoxicity cumulative
- Thyroid disease — dose-dependent hypothyroidism in 20–30% of patients; requires ongoing TSH monitoring
- Unreliable hydration or sodium intake — dehydration, low-sodium diets, and NSAIDs/ACEIs/ARBs precipitate toxicity
- Teratogenicity concern — Ebstein's anomaly risk (0.1–0.2%); cardiac ultrasound required if first-trimester exposure
- +1 more
Valproate
Consider when
- Acute mania or mixed episodes — FDA-approved for mania; rapid-loading strategy (20–30 mg/kg) enables fast onset within days
- Seizure comorbidity with bipolar disorder — broad-spectrum antiepileptic (absence, myoclonic, GTC, partial); dual benefit
- Migraine prophylaxis with mood instability — FDA-approved for migraine prevention; addresses both conditions
- Rapid mood stabilization needed — IV and oral loading available; faster onset than lithium titration or lamotrigine
- +1 more
Consider an alternative when
- Women of childbearing potential — most teratogenic mood stabilizer; neural tube defects 1–2%, IQ reduction 8–10 points; contraindicated in pregnancy for migraine/mania
- Hepatic disease — boxed warning for fatal hepatotoxicity; contraindicated in significant hepatic disease
- Pancreatitis history or risk — boxed warning for life-threatening pancreatitis; can occur at any point during treatment
- Weight gain is a concern — dose-dependent weight gain; worse than lamotrigine or carbamazepine for metabolic profile
- +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
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
Drug-Drug Interactions2 major3 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 | Lithium | Valproate | Olanzapine | Aripiprazole |
|---|---|---|---|---|
| 📊 Efficacy (response rates) | ||||
SchizophreniaEfficacy | — | — | ||
| 🛡️ Acceptability (all-cause discontinuation) | ||||
SchizophreniaAcceptability | — | — | ||
| Axis | Lithium mood-stabilizer | Valproate anticonvulsant-MS | Olanzapine SGA | Aripiprazole 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 | — | |||
Cognitive dulling / anterograde amnesia | — | — | ||
| Metabolic | ||||
Weight gain | ||||
Metabolic (glucose / lipids) | ||||
Hyperammonemia / encephalopathy | — | — | — | |
| Endocrine | ||||
Prolactin elevation | — | — | ||
Renal effects | — | — | — | |
| Autonomic | ||||
Anticholinergic burden | — | — | ||
Orthostatic hypotension | — | — | ||
Sweating | — | — | — | |
| Cardiac | ||||
QTc prolongation | — | — | ||
Cardiac conduction / AV block | — | — | — | |
Blood pressure elevation | — | — | — | |
Heart rate / tachycardia | — | — | — | |
| GI | ||||
Nausea / GI (general) | ||||
| Hepatic | ||||
Liver enzymes / hepatotoxicity | — | — | ||
| Sexual | ||||
Sexual dysfunction | — | |||
| Interactions | ||||
Serotonin syndrome risk | — | — | — | |
CYP interactions / DDI profile | — | — | ||
| Safety | ||||
Bleeding risk | — | — | — | |
Overdose toxicity | — | — | — | |
| Pregnancy | ||||
Teratogenicity | — | — | ||
Lactation / breastfeeding safety | ||||
| Drug-specific / distinctive axes | ||||
Lithium toxicity (BOXED — narrow therapeutic index) only in Lithium | — | — | — | |
Thyroid (hypothyroidism > hyperthyroidism) only in Lithium | — | — | — | |
Hypercalcemia / hyperparathyroidism (distinctive) only in Lithium | — | — | — | |
Encephalopathic syndrome (lithium + neuroleptic) only in Lithium | — | — | — | |
Pseudotumor cerebri only in Lithium | — | — | — | |
Pancreatitis (BOXED) only in Valproate | — | — | — | |
Alopecia (distinctive) only in Valproate | — | — | — | |
Polycystic ovary syndrome / hyperandrogenism (distinctive — women) only in Valproate | — | — | — | |
Hypothermia (distinctive — W&P 5.11) only in Valproate | — | — | — | |