Classification and Adverse Effects of Antipsychotic Medications*

First-generation antipsychotics (dopamine-2 [D2] antagonists)First-generation antipsychotics (dopamine-2 [D2] antagonists)

Chlorpromazine†‡Chlorpromazine†‡

+

+++

+++

++

+++

+++

+++

Prototypic low-potency drug, the first antipsychotic developed

Also available as a rectal suppository

Fluphenazine†‡Fluphenazine†‡

+++

+

+

+++

+/-

-

+/-

Also available as fluphenazine decanoate and enanthate, which are IM depot forms (dose equivalents are not available)Also available as fluphenazine decanoate and enanthate, which are IM depot forms (dose equivalents are not available)

Haloperidol†‡Haloperidol†‡

+++

+

+

+++

+/-

-

++ (if IV)

High potency

Can make some substance intoxications (eg, phencyclidine) worse

Haloperidol decanoate available as IM depotHaloperidol decanoate available as IM depot

Oral liquid concentrate, is rapidly absorbed

No respiratory depression

LoxapineLoxapine

++

++

++

++

+

+

+

—

MolindoneMolindone

++

+

+/-

++

+

+

+

Possibly associated with weight loss

Perphenazine†‡Perphenazine†‡

++

+

++

++

+

+

+

Considered a midpotency antipsychotic

PimozidePimozide

+++

+

+

++

+

+

+

Used for Tourette syndrome

Thioridazine‡Thioridazine‡

+

+++

+++

++

+++

+++

+++

Absolute maximum dose is 800 mg/day because higher doses cause pigmentary retinopathy

Can cause QT prolongation

Thiothixene†‡Thiothixene†‡

+++

+

+

++

+

+

+

Has high incidence of akathisia

Trifluoperazine†‡Trifluoperazine†‡

+++

+

++

+++

+

+

—

—

Second-generation antipsychotics (serotonin-dopamine antagonists)§¶Second-generation antipsychotics (serotonin-dopamine antagonists)§¶

AripiprazoleAripiprazole

+

+

—

-

-

-

+/-

Dopamine-2 partial agonistDopamine-2 partial agonist

Sometimes used to treat major depression as an adjunct to antidepressant

Low risk of sedation and metabolic syndrome

Monitor response in patients taking medications that decrease (carbamazepine) or increase (fluoxetine, paroxetine) plasma levelsMonitor response in patients taking medications that decrease (carbamazepine) or increase (fluoxetine, paroxetine) plasma levels

AsenapineAsenapine

++

+

++

++

+

+

++

Given sublingually with no food to be consumed for 10 minutes afterward (tablet should not be swallowed)

Can cause weight gain, EPS, oral hypoesthesia, and dizziness

BrexpiprazoleBrexpiprazole

+

+

+

+/-

+/-

+/-

+/-

Dopamine-2 and 5HT1A partial agonistDopamine-2 and 5HT1A partial agonist

Sometimes used to treat major depression as an adjunct to antidepressant

Dose titration needed on days 1–8

CariprazineCariprazine

+

+

+/-

+

—

—

—

Partial agonist at D2, 5HT1A, and D3 receptors

Low risk of metabolic syndrome

Somnolence, upset stomach

Dose titration needed on days 1–2

ClozapineClozapine

+/-

+++

++++

+/-

+++

+++

++

First SGA

Effective in patients unresponsive to other antipsychotics

Frequent WBC counts required because agranulocytosis is a risk

Increased risk of seizures, metabolic syndrome, and myocarditis

IloperidoneIloperidone

—

—

—

—

—

—

—

Because of possible QT prolongation and orthostatic hypotension, titrated over 4 days when initiated

LumateperoneLumateperone

+

+/-

+/-

+

+

+

++

Probable antagonist activity at central serotonin 5-HT2A and dopamine D2 receptors Probable antagonist activity at central serotonin 5-HT2A and dopamine D2 receptors

Contraindicated in older patients with dementia-related psychosis

Reduce dose with hepatic impairment

LurasidoneLurasidone

++

+

+/-

+/-

-

+

+/-

Once daily with food

Relatively low risk of sedation and metabolic syndrome

Reduce dose in patients with hepatic impairment

OlanzapineOlanzapine

+

+++

++++

+/-

++

+

++

Available as a monthly depot injection

Most common adverse effects: somnolence, metabolic syndrome, dizziness

Sometimes given IV for agitated patients

PaliperidonePaliperidone

+++

++

+++

+++

-

++

++

Metabolite of risperidone; not extensively metabolized by the liver, thus may be preferred in those with liver impairmentsMetabolite of risperidone; not extensively metabolized by the liver, thus may be preferred in those with liver impairments

Pharmacologically similar to risperidone Pharmacologically similar to risperidone

PimavanserinPimavanserin

+/-

+

+

-

+

++

++

5HT2A inverse agonist

Used for psychosis in Parkinson disease

Not yet approved for schizophrenia in the United States

QuetiapineQuetiapine

+/-

+++

+++

+/-

++

++

+++

Low potency allows for a wide dosing range

Because of sedative effects, sometimes used for insomnia

Sometimes used to treat major depression as adjunct to antidepressant

Dose titration required because of blocking of alpha-2 receptors

Twice-daily dosing required for immediate-release formulation because of a half-life of 6 hours; extended release given once at bedtime

RisperidoneRisperidone

+++

++

+++

+++

+

+

++

EPS more likely at doses > 6 mg; dose-dependent prolactin elevation, or metabolic syndrome; can cause orthostatic hypotension

Available as depot injection (microspheres) every 2 weeks

Ziprasidone†Ziprasidone†

+

+

+/-

+

-

+

+++

Inhibition of serotonin and norepinephrine reuptake, possibly with antidepressant effectsInhibition of serotonin and norepinephrine reuptake, possibly with antidepressant effects

Shortest half-life of second-generation antipsychotics

Requires twice-daily dosing with food

ECG monitoring may be needed when given for agitation

Concomitant use with carbamazepine and ketoconazole should be avoidedConcomitant use with carbamazepine and ketoconazole should be avoided

Muscarinic agonists

Xanomeline-TrospiumXanomeline-Trospium

-

+

+

-

++

+/-

-

M1/M4 agonist

Nausea/vomiting

May cause hypertension