Slide 1. Slide 2. Slide 3. About this module. About this module. Antipsychotics: The Essentials Module 5 A Primer on Selected Antipsychotics
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1 Slide 1 Antipsychotics: The Essentials Module 5 A Primer on Selected Antipsychotics Flavio Guzmán, MD Slide 2 About this module 13 antipsychotics will be studied 3 first generation antipsychotics 10 second generation antipsychotics Plan: Binding profile (highlights, not exhaustive) Basic prescribing information Main clinical features of each AP Slide 3 About this module All antipsychotics mentioned in this presentation are approved for the treatment of schizophrenia.
2 Slide 4 Chlorpromazine (Thorazine) Haloperidol (Haldol) Perphenazine ( Trilafon) Clozapine (Clozaril) Olanzapine (Zyprexa) Risperidone (Risperdal) Paliperidone (INVEGA) Quetiapine (Seroquel) Antipsychotics Ziprasidone (Geodon) Aripiprazole (Abilify) Iloperidone (Fanapt) Asenapine (Saphris) Lurasidone (Latuda) Slide 5 Chlorpromazine One of the first antipsychotics Low potency FGA (high doses required for therapeutic effect) Used as comparator for antipsychotic dose equivalence Slide 6 Chlorpromazine: binding profile - D2 antagonist - H1 antagonist - Alpha 1 antagonist - Muscarinic antagonist - 5HT2A antagonist
3 Slide 7 Chlorpromazine: prescribing facts Dosage range: mg/day Current suggested dosing: mg/day Dosage forms Tablets: 10 mg, 25 mg, 50 mg, 100 mg, 200 mg Capsules: 30 mg, 75 mg, 150 mg Ampul: 25 mg/ml, 1ml, 2ml Liquid: 10 mg/ 5 ml Suppository 25 mg, 100 mg Slide 8 Chlorpromazine: Clinical Profile Advantages Long established use High margin of safety Sedative Disadvantages Tolerability less favorable than safety Generally too sedative for long term use Slide 9 Haloperidol High potency FGA High risk of causing EPS Available as LAI
4 Slide 10 Haloperidol: Binding Profile - Very high affinity for D2 receptors - Affinity for s receptors - No significant action for H1 and M receptors Slide 11 Haloperidol- Prescribing Facts Dose range: 1-40 mg/day orally Efficacy can be obtained with low doses (less than 5 mg/day). Slide 12 Haloperidol- Prescribing Facts Dosage forms: Scored tablets: 0,5 mg, 1 mg, 2 mg, 5 mg, 10 mg, 20 mg. Concentrate: 2 mg/ml Solution: 1 mg/ml Injection 5 mg/ml LAI - Decanoate formulation: 50 mg haloperidol as 70.5 mg/ml haloperidol decanoate. 100 mg haloperidol as mg/ml haloperidol decanoate. Stahl, S M. The Prescriber's Guide. 4thd ed. New York: Cambrigde University Press; 2011
5 Slide 13 Haloperidol: Clinical Profile Advantages Long established use Very useful in psychiatric emergencies Disadvantages Very high liability to produce EPS Perception of dosage higher of what pharmacology suggests Slide 14 Perphenazine Intermediate potency FGA Served as active comparator in the CATIE trial Slide 15 Perphenazine: Binding Profile - Intermediate affinity for D2 receptors - Significant a 1 antagonist action - H1 antagonist
6 Slide 16 Perphenazine: Prescribing Facts Dosage range: mg/day CATIE allowed up to 32 mg/day mg/day in hospitalized patients Dosage forms Tablets: 2 mg, 4 mg, 8 mg, 16 mg Injection: 5 mg/ml Stahl, S M. The Prescriber's Guide. 4thd ed. New York: Cambrigde University Press; 2011 Slide 17 Perphenazine: Clinical Profile Advantages Long established use High margin of safety Better known through its use as active comparator in CATIE Disadvantages Short half-life ( 8-12 hours): ideally is best administered three times daily. Potency and tolerability make easy for EPS to emerge undetected. Slide 18 Clozapine First of the SGAs Unique therapeutic benefits Unique side effects profile
7 Slide 19 Clozapine: Binding Profile - High 5HT2A/D2 ratio - H1 antagonism - Muscarinic antagonism a 1 antagonism - 5HT2C antagonism Slide 20 Clozapine: Binding Profile - D3 and D4 antagonist - 5HT1A partial agonist Slide 21 Clozapine: Prescribing Facts Dosage range: mg/day In some cases: higher than 500 mg/day (risk of seizures) Dosage forms: Tablets: 12.5 mg, 25 mg (scored), 50 mg, 100 mg (scored) Orally disintegrating tablets: 12.5 mg, 25 mg, 50 mg, 100 mg Metabolized primarily by CYP1A2, with additional contributions by CYP2C19, CYP2D6 and CYP3A4 Stahl, S M. The Prescriber's Guide. 4thd ed. New York: Cambrigde University Press; 2011
8 Slide 22 Clozapine: Clinical Profile Effective for treatment-resistant schizophrenia. Reduces violence and persistent aggression in schizophrenia. Long-term treatment associated with reduction of risk of suicidal behaviors. Hennen J, Baldessarini RJ. Suicidal risk during treatment with clozapine: a meta-analysis. Schizophrenia research 2005 Conley RR, Buchanan RW. Evaluation of treatment-resistant schizophrenia. Schizophr Bull 1997 Slide 23 Clozapine Adverse Effects Profile One of the antipsychotics with the lowest EPS risk One of the antipsychotics with the highest metabolic risk Risk of agranulocytosis Dose-dependent seizure risk Can be very sedating Slide 24 Olanzapine SGA less dirty than clozapine. Available in combination with fluoxetine: OFC Dosage forms include parenteral formulations
9 Slide 25 Olanzapine Binding Profile - High 5HT2A/D2 ratio - H1 antagonist - Muscarinic antagonist a 1 antagonist - 5HT2C antagonist Slide 26 Olanzapine- Prescribing Facts Dosage range: mg/day Dosage forms: Tablets: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg Orally disintegrating tablets: 5 mg, 10 mg, 15 mg, 20 mg OFC capsule: 6 mg/ 25 mg, 6 mg /50 mg, 12 mg/25 mg, 12 mg/50 mg IM formulation: 5 mg/ml, each vial contains 10 mg (available in some countries) LAI: olanzapine pamoate: 150 mg, 300 mg, 210 mg, 405 mg Stahl, S M. The Prescriber's Guide. 4thd ed. New York: Cambrigde University Press; 2011 Slide 27 Olanzapine Clinical Profile Olanzapine/fluoxetine combination was the first drug approved for bipolar depression. Associated with less EPS than FGAs. Weight gain is problematic with long term use. Can be very sedating. Janicak, P G., Marder S R., and. Pavuluri M N. Principles and Practice of Psychopharmacotherapy. 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2010.
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