Skip to Main Content

We have a new app!

Take the Access library with you wherever you go—easy access to books, videos, images, podcasts, personalized features, and more.

Download the Access App here: iOS and Android. Learn more here!



ACEI: angiotensin-converting enzyme inhibitor

ARB: angiotensin receptor blocker

COX-2: cyclooxygenase 2

CV: cardiovascular

DA: dopamine

DRP: dementia-related psychosis

ECG: electrocardiogram

ECT: electroconvulsive therapy

eGFR: estimated glomerular filtration rate

ENaC: epithelial Na+ channel

EPS: extrapyramidal symptom

FGA: first-generation antipsychotic

GFR: glomerular filtration rate

GI: gastrointestinal

GPCR: G protein-coupled receptor

GSK: glycogen synthase kinase

5HT: serotonin

Ikr: inwardly rectifying K+ channels

LAI: long-acting injectable

Li+: lithium

LSD: lysergic acid diethylamide

MCM: major congenital malformations

NDI: nephrogenic diabetes insipidus

NMDA: N-methyl-D-aspartate

NMS: neuroleptic malignant syndrome

ODT: oral dissolving tablet

PDP: Parkinson’s disease psychosis

Pgp: P-glycoprotein

PI: phosphatidylinositol

PK_: protein kinase _, as in PKA, PKB, PKC

PP2A: protein phosphatase 2A

SCD: sudden cardiac death

SGA: second-generation antipsychotic

TAAR1: trace amine-associated receptor 1

TD: tardive dyskinesia

TSH: thyrotropin (thyroid-stimulating hormone)

VMAT2: vesicular monoamine transporter 2

VPA: valproic acid


Psychosis is a symptom of numerous psychiatric illnesses, characterized by a distorted or nonexistent sense of reality or by disorganized behavior or speech. Psychotic disorders have different etiologies, each of which demands a unique treatment approach. Common psychotic disorders include mood disorders (major depression or mania) with psychotic features, substance-induced psychosis, dementia with psychotic features, delirium with psychotic features, brief psychotic disorder, delusional disorder, schizoaffective disorders, and schizophrenia.

The worldwide schizophrenia point prevalence has remained relatively constant, with the global estimate of 0.28% remaining unchanged from 1990 to 2016; however, the number of individuals suffering from schizophrenia rose nearly 60% due to population increases (Charlson et al., 2018). Older sources cite schizophrenia prevalence rates of 1%, but a 2018 analysis of 101 studies noted that higher study quality was associated with a lower estimated prevalence of psychotic disorders (P < .001) (Moreno-Kustner et al., 2018). Schizophrenia is considered the prototypic disorder for understanding chronic psychosis, but patients with schizophrenia exhibit features not seen in other psychotic illnesses. The positive symptoms of psychosis include hallucinations, delusions, disorganized speech, and disorganized or agitated behavior. These positive psychotic symptoms are found individually, and occasionally together, in all psychotic disorders and are typically responsive to pharmacotherapy. Schizophrenia patients also suffer from negative symptoms (apathy, avolition, diminished expression, reduced social drive) and cognitive deficits.

Neurotransmitter Bases for Psychosis

Dysfunction in cholinergic, glutamatergic, serotonergic, GABA-ergic, and dopaminergic systems is implicated in psychosis (McCutcheon et al., 2019). That excessive dopamine (DA) neurotransmission is linked to positive psychosis symptoms has been known for over 60 years since Carlsson deduced that postsynaptic DA receptor antagonism was the common mechanism for haloperidol and chlorpromazine’s therapeutic effects and for their ability to induce parkinsonism. This insight informed the development of antipsychotics that act at D2 receptors including first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) that possess D2 antagonism and newer agents with D2 partial agonism ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.