1. Antipsychotic Agents and Their Use in Schizophrenia
Chapter 31
Antipsychotic Agents and Their Use in Schizophrenia 1

2. Antipsychotic Agents Chemically diverse group of compounds
Used for diverse spectrum of psychotic disorders
Schizophrenia, delusional disorders, bipolar disorders, depressive psychoses, drug-induced psychoses
Also used to suppress emesis and to treat Tourette’s syndrome and Huntington’s chorea
Should not be used to treat dementia in the older adult 2

3. Antipsychotic Agents
First-generation antipsychotics (FGAs) or conventional antipsychotics
Block receptors for dopamine in CNS
Cause serious movement disorders (extrapyramidal symptoms [EPS])
Second-generation antipsychotics (SGAs) or atypical antipsychotics
Produce only moderate blockade of dopamine receptors; stronger blockade for serotonin
Fewer EPS 3

4. Antipsychotic Agents
Top-selling medications in the United States in 2009
Total sales of $14.6 billion
FGA higher risk of EPS
SGA higher risk of metabolic effects (diabetes, dyslipidemia) 4

5. Clinical Presentation
Disordered thinking and reduced ability to comprehend reality
Three types of symptoms
Positive symptoms and negative symptoms
Cognitive symptoms
Acute episodes
Residual symptoms
Long-term course
Causes 5

6. Classification Classification by potency Chemical classification
Low potency: chlorpromazine HCl (Thorazine)
Medium potency: loxapine (Loxitane)
High potency: haloperidol (Haldol)
Chemical classification
Six major chemical categories
Drugs in all groups equivalent with respect to antipsychotic actions 6

7. Adverse Effects
EPS (Extra-pyramidal symptoms) include (treatment for these is an anticholinergic drug like diphenhydramine or benztropine)
Acute dystonic reaction: laryngospasm, facial spam, and oculogyric crisis
Akathesia
Parkinsonism
Tardive dyskinesia: wormlike movements of tongue and face 7

8. Adverse Effects Other adverse effects Neuroleptic malignant syndrome
Rare but serious reaction
Risk of death without treatment
Sweating, rigidity, sudden high fever, autonomic instability
Anticholinergic effects
See Table 31-3.
Orthostatic hypotension (alpha 1 blockade): dizziness/lightheadedness subsides in 1-2 weeks 8

9. Adverse Effects Other adverse effects (cont’d)
Sedation (histamine blockade)
Neuroendocrine effects: gynecomastia, galactorrhea, menstrual irregularity (prolactin increase)
Seizures
Sexual dysfunction
Dermatologic effects
Agranulocytosis
Severe dysrhythmias 9

10. Drug Interactions Anticholinergic drugs CNS depressants
Intensify the anticholinergic effect
CNS depressants
Can intensify the depressant effect
Levodopa and direct dopamine receptor agonists
May counteract the antipsychotic effects of neuroleptics 10

11. Atypical Antipsychotic Agents
Introduced in the 1990s
Less risk of EPS than FGAs
Increased risk of weight gain, diabetes, and dyslipidemia
Examples: clozapine and other atypical antipsychotics 11

12. Atypical Antipsychotics (a few names)
Risperidone (Risperdal)
Olanzapine (Zyprexa)
Quetiapine (Seroquel)
Aripiprazole (Abilify) 12

13. Depot Preparations
Depot antipsychotics: long-acting, injectable formulations used for long-term maintenance therapy of schizophrenia
No evidence that depot preparations pose an increased risk of side effects
Three depot preparations available
Haloperidol decanoate (Haldol Decanoate)
Fluphenazine decanoate (Prolixin Decanoate)
Risperidone microspheres (Risperdal Consta) 13

14. Schizophrenia Drug Therapy
Three major objectives
Suppression of acute episodes
Prevention of acute exacerbations
Maintenance of the highest possible level of functioning
Drug selection
Dosing
Route
Oral (tablets, capsules, liquids)
Intramuscular 14

15. Schizophrenia Drug Therapy
Most FGAs and SGAs are equally effective, except for clozapine, which is more effective than the rest
FGAs: significant risk of EPS
SGAs: risk of metabolic effects
FGAs: cost 10 times less than SGAs 15

16. Schizophrenia Drug Therapy
Dosing
Highly individualized
Older adult patients require relatively small doses.
Size and timing likely to be changed over course of therapy
Routes
Oral (preferred)
Intramuscular 16