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Abbreviations
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
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TREATMENT OF PSYCHOSIS
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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.
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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.
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Neurotransmitter Bases for Psychosis
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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 ...