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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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