Anti-Psychotics

Used for Schizophrenia and Bipolar Disease (however, last choice for BP disease)
Do NOT use anti-psychotics for anxiety, PTSD, insomnia, dementia, delirium or acute agitation

Schizophrenia
Dopamine, Ser, Ach, glutamate and GABA
Hyper dopamine + symptoms (hallucinations)
Hypo dopamine - symptoms

MOA of anti-psychotics (common MOA): Dopamine Antagonism. Prevents DA from acting on post-synaptic
D2 receptors. Mesolimbic pathway treats + symptoms (blocking DA).
MOA other receptor involvement: 5HT2A antagonism is common with SGAs (2nd gen). May also act on alpha
1, histamine 1 or M1 receptors (varies among agents)
Black Box for ALL: elderly patients with dementia-related psychosis treated with these drugs are at high risk
of death. Not approved for dementia-related psychosis!!
Side Effects: EPS (extrapyramidal symptoms: akathisia, Dystonia, Pseudoparkinsonism, Tardive Dyskinesia),
Orthostatic hypotension, QTc inverval prolongation, hyperprolactinemia, anticholinergic effects (worsen
glaucoma/dry eyes, confusion, falls, delirium, dry),

First Generation Anti-Psychotics azines

Characteristics: Increased chance of EPS (potent D2 antagonism), Lower incidence of metabolic ADEs, may
worsen negative symptoms (D2 antagonism in the mesocortical pathways and lack of 5HT2 anatgonism)
Chlorpromazine (Throazine) * low potency (higher doses needed but higher anticholinergic effects,
sedation, and orthostatis)
Fluphenazine (Prolixin) * high potency lower doses, but higher movement related effects (EPS)
Haloperidol (Haldol) * high potency lower doses, but higher movement
Loxapine
Perphenazine
Thiordazine
Thiothixene BBW for QTc prolongation (torsades) monitor EKG and K and Mg
Trifluoperazine CI in liver disease
Second Generation Antipsychotics
Characteristics: less potent D2 antagonism, shorter duration of receptor occupancy (lower EPS), 5HT2A
antagonism is common MOA, increased metabolic effects, newer agents exhibit D2 partial agonism (Arip,
Brex, Cari) which can reduce EPS
Side effects: less EPS but more metabolic effects: hyperlipidemia, weight gain, glucose intolerance (DM2),
HTN
Drug Interactions: mixing 2+ drugs can lead to anticholinergic effects, over sedation, QTc prolongation. CYP
interactions (both generations) they are metabolized by CYP1A2, 2D6, 3A4 so must consider dose reductions.
Hydrocarbons produced from cigs induce CYP1A2.

Clozapine (Clozaril) ortho hypotension, REMS program?, Treatment resistance schizophrenia (need
a minimum of trying at least 2 other APs), Low potency at D2receptor and high affinity for 5HT2A
receptor. Very low EPS and may improved TD. Antagonism at alpha 1, H1, M2.
o BBW: dementia related mortality, severe neutropenia, orthostatic hypotension, myocarditis,
seizures
o Dose related effects: neutropenia, ortho hypo, bradycardia, syncope, seizures, initiate at
low dose and increase will reduce these
o REMS program: Risk Evaluation and Mitigation Strategy program: patient, prescriber and
pharmacy must be registered, outlines absolute neutrophil count. ANC of 1.5? to start?
Monitor ANC basically
o Other effects: lowest EPS and highest metabolic effects. Constipation. Sialorrhea (drooling)
Aripiprazole (Abilify) partial D2 agonism, higher incidence of akathisa BBW: SI in children and
adolescents
Lurasidone (Latuda)- ONLY works with food-350 calories, BBW SI kids/adol
Olanzapine (Zyprexa)- BBW for post-injection delirium/sedation syndrome with LAI (long acting
injectibles)
Paliperidone (Invega)- metabolite of Risperidone
Ziprasidone (Geodon) take with 500 calories
Risperidone (Risperdal)- Orthostasis, ortho hypotension, HIGH incidence of hyperprolactinemia (high
D2 affinity)
 Quetiapine (Seroquel)- ortho hypotension, BBW for SI
Iloperidone - ortho hypotension,
Cariprazine
Brexpiprazole
Asenapine

Long Acting Injectable Anti-Psychotics

Improve adherence
Use in patients with problems of relapsing or non-adherence or if they prefer them
Not typically first line
Fluphenazine Decanoate
Haloperidol Decanoate
Rispiridone (Risperdal Consta)
Paliperidone (invega Sustenna)
Olazapine
Aripiprazole (Abilify Maintena)